U.S. patent application number 15/526219 was filed with the patent office on 2018-06-21 for peptides derived from acinetobacter baumannii and their use in vaccination.
The applicant listed for this patent is Evaxion Biotech ApS. Invention is credited to Andreas Holm Mattsson, Niels Iversen Moller.
Application Number | 20180169211 15/526219 |
Document ID | / |
Family ID | 52023158 |
Filed Date | 2018-06-21 |
United States Patent
Application |
20180169211 |
Kind Code |
A1 |
Moller; Niels Iversen ; et
al. |
June 21, 2018 |
Peptides derived from acinetobacter baumannii and their use in
vaccination
Abstract
The present invention relates to proteins derived from
Acinetobacter Baumanii, nucleic acids encoding the proteins,
antibodies specific for the proteins as well as methods of therapy,
prophylaxis, and diagnosis that utilize the proteins, nucleic
acids, and antibodies.
Inventors: |
Moller; Niels Iversen;
(Copenhagen K, DK) ; Mattsson; Andreas Holm;
(Copenhagen N, DK) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
Evaxion Biotech ApS |
Copenhagen N |
|
DK |
|
|
Family ID: |
52023158 |
Appl. No.: |
15/526219 |
Filed: |
November 13, 2015 |
PCT Filed: |
November 13, 2015 |
PCT NO: |
PCT/EP2015/076598 |
371 Date: |
May 11, 2017 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
G01N 2469/20 20130101;
A61K 39/104 20130101; A61K 2039/55505 20130101; G01N 2333/22
20130101; C07K 14/212 20130101; A61K 2039/55566 20130101; A61K
2039/543 20130101 |
International
Class: |
A61K 39/104 20060101
A61K039/104; C07K 14/21 20060101 C07K014/21 |
Foreign Application Data
Date |
Code |
Application Number |
Nov 13, 2014 |
EP |
14193008.1 |
Claims
1. A polypeptide comprising a) an amino acid sequence selected from
the group consisting of any one of SEQ ID NOs: 1-30, or b) an amino
acid sequence consisting of at least 30 contiguous amino acid
residues from any one of SEQ ID NOs: 1-30, or c) an amino acid
sequence having a sequence identity of at least 80% with the amino
acid sequence of a), or d) an amino acid sequence having a sequence
identity of at least 80% with the amino acid sequence of b) said
polypeptide being antigenic in a mammal.
2. The polypeptide according to claim 1, wherein the at least 30
contiguous amino acids are at least or exactly or at most 31, at
least or exactly or at most 32, at least or exactly or at most 33,
at least or exactly or at most 34, at least or exactly or at most
35 and at least or exactly or at most 36, at least or exactly or at
most 37, at least or exactly or at most 38, at least or exactly or
at most 39, at least or exactly or at most 40, at least or exactly
or at most 41, at least or exactly or at most 42, at least or
exactly or at most 43, at least or exactly or at most 44, at least
or exactly or at most 45, at least or exactly or at most 46, at
least or exactly or at most 47, at least or exactly or at most 48,
at least or exactly or at most 49, at least or exactly or at most
50, at least or exactly or at most 51, at least or exactly or at
most 52, at least or exactly or at most 53, at least or exactly or
at most 54, at least or exactly or at most 55 and at least or
exactly or at most 56, at least or exactly or at most 57, at least
or exactly or at most 58, at least or exactly or at most 59, or at
least or exactly or at most 60 contiguous amino acid residues.
3. The polypeptide according to claim 1 or 2, wherein the sequence
identity with the amino acid sequence of a) is at least 85%, at
least 90%, at least 91%, at least 92%, at least 93%, at least 94%,
at least 95%, at least 96%, at least 97%, at least 98%, and at
least 99%.
4. The polypeptide according to claim 1 or 2, wherein the sequence
identity with the amino acid sequence of b) is at least 85%, at
least 90%, at least 91%, at least 92%, at least 93%, at least 94%,
at least 95%, at least 96%, at least 97%, at least 98%, and at
least 99%.
5. The polypeptide according to claim 1, wherein the at least 30
contiguous amino acid residues has an N-terminal amino acid residue
corresponding to any one of amino acid residues 1, 2, 3, 4, 5, 6,
7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40,
42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, and 56 in
any one of SEQ ID NOs: 1-30 or any one of amino acid residues 57,
58, 59, 60, 61, and 62 in any one of SEQ ID NOs: 2-30, or any one
of amino acid residues 63, 64, 65, 66, 67, 68, and 69 in any one of
SEQ ID NOs: 4-30, or any one of amino acid residues 70, 71, 72, 73,
74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90,
91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, and 104 in
any one of SEQ ID NOs: 5-30, or any one of amino acid residues 105,
106, 107, 108, 109, and 110 in any one of SEQ ID NOs: 6-30, or any
one of amino acid residues 111, 112, 113, 114, 115, 116, 117, 118,
119, 120, 121 and 122 in any one of SEQ ID NOs: 7-30, or any one of
amino acid residues 123, 124, 125, 126, 127, 128, 129, 130, 131,
132, 133, 134, and 135 in any one of SEQ ID NOs: 8-30, or any one
of amino acids 136, 137, 138, 139, 140, 141, 142, 143, 144, 145,
146, 147, 148, 149, 150, 151, 152, 153, 154, and 155 in any one of
SEQ ID NOs: 9-30, or any one of amino acid residues 156, 157, and
158 in any one of SEQ ID NOs: 10-30, or any one of amino acid
residues 159, 160, 161, and 162 in any one of SEQ ID NOs: 11-30, or
any one of amino acid residues 163, 164, 165, 166, 167, 168, 169,
170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182,
183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195,
196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208,
209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221,
222, 223, 224, 225, and 226 in any one of SEQ ID NOs: 12-30, or any
one of amino acid residues 227, 228, 229, 230, 231, 232, 233, and
234 in any one of SEQ ID NOs: 13-30, or any one of amino acid
residues 235, 236, 237, 238, 239, 240, 241, 242, 243, 244, 245,
246, 247, 248, and 249 in any one of SEQ ID NOs: 14-30, or any one
of amino acid residues 250, 251, 252, 253, 254, 255, 256, 257, 258,
259, 260, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281,
282, 283, 284, 285, 286, 287, 288, 289, and 290 in any one of SEQ
ID NOs: 15-30, or any one of amino acid residues 291, 292, 293,
294, 295, 296, 297, 298, 299, 300, 301, 302, 303, 304, 305, 306,
307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318, 319,
320, 321, 322, 323, 324, 325, 326, 327, 328, 329, 330, 331, 332,
333, 334, 335, 336, 337, 338, 339, 340, 341, 342, 343, 344, 345,
346, 347, 348, 349, 350, 351, and 352 in any one of SEQ ID NOs:
16-30, or any one of amino acid residues 353, 354, 355, 356, 357,
358, 359, 360, 361, 362, and 363 in any one of SEQ ID NOs: 17-30,
or any one of amino acid residues 364, 365, 366, 367, 368, 369,
370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380, 381, 382,
383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394, 395,
396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408,
409, 410, 411, 412, 413, 414, 415, and 416 in any one of amino acid
residues in any one of SEQ ID NOs: 18-30, or any one of amino acid
residues 417, 418, 419, 420, 421, 422, 423, 424, 425, 426, 427,
428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440,
and 441 in any one of SEQ ID NOs: 19-30, or any one of amino acid
residues 442, 443, 444, 445, 446, 447, 448, 449, 450, 451, 452,
453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464, 465,
466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478,
479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491,
492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504,
505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517,
518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528, 529, 530,
531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541, 542, 543,
544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554, 555, 556,
557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567, 568, 569,
570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580, 581, 582,
583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593, 594, 595,
596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606, 607, 608,
609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619, 620, 621,
622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632, 633, 634,
635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646, 647,
648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660,
661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673,
674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686,
687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699,
700, 701, 702, 703, 704, 705, 706, and 707 in any one of SEQ ID
NOs: 20-30, or any one of amino acid residues 708, 709, 710, 711,
712, 713, 714, 715, 716, 717, 718, 719, 720, 721, 722, and 723 in
any one of SEQ ID NOs: 21-30, or amino acid residue 724 in any one
of SEQ ID NOs: 22-30, or any one of amino acid residues 725, 726,
727, 728, 729, 730, 731, 732, 733, 734, 735, 736, 737, 738, 739,
740, 741, 742, 743, 744, 745, 746, 747, 748, 749, and 750 in any
one of SEQ ID NOs: 23-30, or any one of amino acid residues 751,
752, 753, 754, 755, 756, 757, 758, 759, 760, 761, 762, 763, 764,
765, 766, 767, 768, 769, 770, 771, 772, 773, 774, 775, 776, 777,
778, 779, 780, 781, 782, 783, 784, 785, 786, 787, 788, 789, 790,
791, 792, 793, 794, 795, 796, 797, 798, 799, 800, 801, 802, 803,
804, 805, 806, 807, 808, 809, 810, 811, 812, 813, 814, 815, 816,
817, 818, 819, 820, 821, 822, 823, 824, 825, 826, 827, 828, 829,
830, 831, 832, 833, 834, 835, 836, 837, 838, 839, 840, 841, 842,
843, 844, 845, 846, 847, 848, 849, 850, 851, 852, 853, 854, 855,
856, 857, 858, 859, 860, 861, 862, 863, 864, 865, 866, 867, 868,
869, 870, 871, 872, 873, 874, 875, 876, 877, 878, 879, 880, 881,
882, 883, 884, 885, 886, 887, 888, 889, 890, 891, 892, 893, 894,
895, 896, 897, 898, 899, 900, 901, and 902 in any one of SEQ ID
NOs: 24-30, or any one of amino acid residues 903, 904, 905, 906,
907, 908, 909, 910, 911, 912, 913, 914, 915, 916, 917, 918, 919,
920, 921, 922, 923, 924, 925, 926, 927, 928, 929, 930, 931, 932,
933, 934, 935, 936, 937, 938, 939, 940, 941, 942, 943, 944, 945,
946, 947, 948, 949, 950, 951, 952, 953, 954, 955, 956, 957, 958,
959, 960, 961, 962, 963, 964, 965, 966, 967, 968, 969, and 970 in
any one of SEQ ID NOs: 25-30, or any one of amino acid residues
971, 972, 973, 974, 975, 976, 977, 978, 979, 980, 981, 982, 983,
984, 985, 986, 987, 988, 989, 990, 991, 992, 993, 994, 995, 996,
997, 998, 999, 1000, 1001, 1002, 1003, 1004, 1005, 1006, 1007,
1008, 1009, 1010, 1011, 1012, 1013, 1014, 1015, 1016, 1017, 1018,
1019, 1020, 1021, 1022, 1023, 1024, 1025, 1026, 1027, 1028, 1029,
1030, 1031, 1032, 1033, 1034, 1035, 1036, 1037, 1038, 1039, 1040,
1041, 1042, 1043, 1044, 1045, 1046, 1047, 1048, 1049, 1050, 1051,
1052, 1053, 1054, 1055, 1056, 1057, 1058, 1059, 1060, 1061, 1062,
1063, 1064, 1065, 1066, and 1067 in any one of SEQ ID NOs: 26-30,
or any one of amino acid residues 1068, 1069, 1070, 1071, 1072,
1073, 1074, 1075, 1076, 1077, 1078, 1079, 1080, 1081, 1082, 1083,
1084, 1085, 1086, 1087, 1088, 1089, 1090, 1091, 1092, 1093, 1094,
1095, 1096, 1097, 1098, 1099, 1100, 1101, 1102, 1103, 1104, 1105,
and 1106 in any one of SEQ ID NOs: 27-30, or any one of amino acid
residues 1107, 1108, 1109, 1110, 1111, 1112, 1113, 1114, 1115,
1116, 1117, 1118, 1119, 1120, 1121, 1122, 1123, 1124, 1125, 1126,
1127, 1128, 1129, 1130, 1131, 1132, 1133, 1134, 1135, 1136, 1137,
1138, 1139, 1140, 1141, 1142, 1143, 1144, 1145, 1146, 1147, 1148,
1149, 1150, 1151, 1152, 1153, 1154, 1155, 1156, 1157, 1158, 1159,
1160, 1161, 1162, 1163, 1164, 1165, 1166, 1167, 1168, 1169, 1170,
1171, 1172, 1173, 1174, 1175, 1176, 1177, 1178, 1179, 1180, 1181,
1182, 1183, 1184, 1185, 1186, 1187, 1188, 1189, 1190, 1191, 1192,
1193, 1194, 1195, 1196, 1197, 1198, 1199, 1200, 1201, 1202, 1203,
1204, 1205, 1206, 1207, 1208, 1209, 1210, 1211, 1212, 1213, 1214,
1215, 1216, 1217, 1218, 1219, 1220, 1221, 1222, 1223, and 1224 in
any one of SEQ ID NOs: 28-30, or any one of amino acid residues
1225, 1226, 1227, 1228, 1229, 1230, 1231, 1232, 1233, 1234, 1235,
1236, 1237, 1238, 1239, 1240, 1241, 1242, 1243, 1244, 1245, 1246,
1247, 1248, 1249, 1250, 1251, 1252, 1253, 1254, 1255, 1256, 1257,
1258, 1259, 1260, 1261, 1262, 1263, 1264, 1265, 1266, 1267, 1268,
1269, 1270, 1271, 1272, 1273, 1274, 1275, 1276, 1277, 1278, 1279,
and 1280 in any one of SEQ ID NOs: 29-30, or any one of amino acid
residues 1281, 1282, 1283, 1284, 1285, 1286, 1287, 1288, 1289,
1290, 1291, 1292, 1293, 1294, 1295, 1296, 1297, 1298, 1299, 1300,
1301, 1302, 1303, 1304, 1305, 1306, 1307, 1308, 1309, 1310, 1311,
1312, 1313, 1314, 1315, 1316, 1317, 1318, 1319, 1320, 1321, 1322,
1323, 1324, 1325, 1326, 1327, 1328, 1329, 1330, 1331, 1332, 1333,
1334, 1335, 1336, 1337, 1338, 1339, 1340, 1341, 1342, 1343, 1344,
1345, 1346, 1347, 1348, 1349, 1350, 1351, 1352, 1353, 1354, 1355,
1356, 1357, 1358, 1359, 1360, 1361, 1362, 1363, 1364, 1365, 1366,
1367, 1368, 1369, 1370, 1371, 1372, 1373, 1374, 1375, 1376, 1377,
1378, 1379, 1380, 1381, 1382, 1383, 1384, 1385, 1386, 1387, 1388,
1389, 1390, 1391, 1392, 1393, 1394, 1395, 1396, 1397, 1398, 1399,
1400, 1401, 1402, 1403, 1404, 1405, 1406, 1407, 1408, 1409, 1410,
1411, 1412, 1413, 1414, 1415, 1416, 1417, 1418, 1419, 1420, 1421,
1422, 1423, 1424, 1425, 1426, 1427, 1428, 1429, 1430, 1431, 1432,
1433, 1434, 1435, 1436, 1437, 1438, 1439, 1440, 1441, 1442, 1443,
1444, 1445, 1446, 1447, 1448, 1449, 1450, 1451, 1452, 1453, 1454,
1455, 1456, 1457, 1458, 1459, 1460, 1461, 1462, 1463, 1464, 1465,
1466, 1467, 1468, 1469, 1470, 1471, 1472, 1473, 1474, 1475, 1476,
1477, 1478, 1479, 1480, 1481, 1482, 1483, 1484, 1485, 1486, 1487,
1488, 1489, 1490, 1491, 1492, 1493, 1494, 1495, 1496, 1497, 1498,
1499, 1500, 1501, 1502, 1503, 1504, 1505, 1506, 1507, 1508, 1509,
1510, 1511, 1512, 1513, 1514, 1515, 1516, 1517, 1518, 1519, 1520,
1521, 1522, 1523, 1524, 1525, 1526, 1527, 1528, 1529, 1530, 1531,
1532, 1533, 1534, 1535, 1536, 1537, 1538, 1539, 1540, 1541, 1542,
1543, 1544, 1545, 1546, 1547, 1548, 1549, 1550, 1551, 1552, 1553,
1554, 1555, 1556, 1557, 1558, 1559, 1560, 1561, 1562, 1563, 1564,
1565, 1566, 1567, 1568, 1569, 1570, 1571, 1572, 1573, 1574, 1575,
1576, 1577, 1578, 1579, 1580, 1581, 1582, 1583, 1584, 1585, 1586,
1587, 1588, 1589, 1590, 1591, 1592, 1593, 1594, 1595, 1596, 1597,
1598, 1599, 1600, 1601, 1602, 1603, 1604, 1605, 1606, 1607, 1608,
1609, 1610, 1611, 1612, 1613, 1614, 1615, 1616, 1617, 1618, 1619,
1620, 1621, 1622, 1623, 1624, 1625, 1626, 1627, 1628, 1629, 1630,
1631, 1632, 1633, 1634, 1635, 1636, 1637, 1638, 1639, 1640, 1641,
1642, 1643, 1644, 1645, 1646, 1647, 1648, 1649, 1650, 1651, 1652,
1653, 1654, 1655, 1656, 1657, 1658, 1659, 1660, 1661, 1662, 1663,
1664, 1665, 1666, 1667, 1668, 1669, 1670, 1671, 1672, 1673, 1674,
1675, 1676, 1677, 1678, 1679, 1680, 1681, 1682, 1683, 1684, 1685,
1686, 1687, 1688, 1689, 1690, 1691, 1692, 1693, 1694, 1695, 1696,
1697, 1698, 1699, 1700, 1701, 1702, 1703, 1704, 1705, 1706, 1707,
1708, 1709, 1710, 1711, 1712, 1713, 1714, 1715, 1716, 1717, 1718,
1719, 1720, 1721, 1722, 1723, 1724, 1725, 1726, 1727, 1728, 1729,
1730, 1731, 1732, 1733, 1734, 1735, 1736, 1737, 1738, 1739, 1740,
1741, 1742, 1743, 1744, 1745, 1746, 1747, 1748, 1749, 1750, 1751,
1752, 1753, 1754, 1755, 1756, 1757, 1758, 1759, 1760, 1761, 1762,
1763, 1764, 1765, 1766, 1767, 1768, 1769, 1770, 1771, 1772, 1773,
1774, 1775, 1776, 1777, 1778, 1779, 1780, 1781, 1782, 1783, 1784,
1785, 1786, 1787, 1788, 1789, 1790, 1791, 1792, 1793, 1794, 1795,
1796, 1797, 1798, 1799, 1800, 1801, 1802, 1803, 1804, 1805, 1806,
1807, 1808, 1809, 1810, 1811, 1812, 1813, 1814, 1815, 1816, 1817,
1818, 1819, 1820, 1821, 1822, 1823, 1824, 1825, 1826, 1827, 1828,
1829, 1830, 1831, 1832, 1833, 1834, 1835, 1836, 1837, 1838, 1839,
1840, 1841, 1842, 1843, 1844, 1845, 1846, 1847, 1848, 1849, 1850,
1851, 1852, 1853, 1854, 1855, 1856, 1857, 1858, 1859, 1860, 1861,
1862, 1863, 1864, 1865, 1866, 1867, 1868, 1869, 1870, 1871, 1872,
1873, 1874, 1875, 1876, 1877, 1878, 1879, 1880, 1881, 1882, 1883,
1884, 1885, 1886, 1887, 1888, 1889, 1890, 1891, 1892, 1893, 1894,
1895, 1896, 1897, 1898, 1899, 1900, 1901, 1902, 1903, 1904, 1905,
1906, 1907, 1908, 1909, 1910, 1911, 1912, 1913, 1914, 1915, 1916,
1917, 1918, 1919, 1920, 1921, 1922, 1923, 1924, 1925, 1926, 1927,
1928, 1929, 1930, 1931, 1932, 1933, 1934, 1935, 1936, 1937, 1938,
1939, 1940, 1941, 1942, 1943, 1944, 1945, 1946, 1947, 1948, 1949,
1950, 1951, 1952, 1953, 1954, 1955, 1956, 1957, 1958, 1959, 1960,
1961, 1962, 1963, 1964, 1965, 1966, 1967, 1968, 1969, 1970, 1971,
1972, 1973, 1974, 1975, 1976, 1977, 1978, 1979, 1980, 1981, 1982,
1983, 1984, 1985, 1986, 1987, 1988, 1989, 1990, 1991, 1992, 1993,
1994, 1995, 1996, 1997, 1998, 1999, 2000, 2001, 2002, 2003, 2004,
2005, 2006, 2007, 2008, 2009, 2010, 2011, 2012, 2013, 2014, 2015,
2016, 2017, 2018, 2019, 2020, 2021, 2022, 2023, 2024, 2025, 2026,
2027, 2028, 2029, 2030, 2031, 2032, 2033, 2034, 2035, 2036, 2037,
2038, 2039, 2040, 2041, 2042, 2043, 2044, 2045, 2046, 2047, 2048,
2049, 2050, 2051, 2052, 2053, 2054, 2055, 2056, 2057, 2058, 2059,
2060, 2061, 2062, 2063, 2064, 2065, 2066, 2067, 2068, 2069, 2070,
2071, 2072, 2073, 2074, 2075, 2076, 2077, 2078, 2079, 2080, 2081,
2082, 2083, 2084, 2085, 2086, 2087, 2088, 2089, 2090, 2091, 2092,
2093, 2094, 2095, 2096, 2097, 2098, 2099, 2100, 2101, 2102, 2103,
2104, 2105, 2106, 2107, 2108, 2109, 2110, 2110, 2111, 2112, 2113,
2114, 2115, 2116, 2117, 2118, 2119, 2120, 2121, 2122, 2123, 2124,
2125, 2126, 2127, 2128, 2129, 2130, 2131, 2132, 2133, 2134, 2135,
2136, 2137, 2138, 2139, 2140, 2141, 2142, 2143, 2144, 2145, 2146,
2147, 2148, 2149, 2150, 2151, 2152, 2153, 2154, 2155, 2156, 2157,
2158, 2159, 2160, 2171, 2172, 2173, 2174, 2175, 2176, 2177, 2178,
2179, 2180, 2181, 2182, 2183, 2184, 2185, 2186, 2187, 2188, 2189,
2190, 2191, 2192, 2193, 2194, 2195, 2196, 2197, 2198, 2199, 2200,
2201, 2202, 2203, 2204, 2205, 2206, 2207, 2208, 2209, 2210, 2211,
2212, 2213, 2214, 2215, 2216, 2217, 2218, 2219, 2220, 2221, 2222,
2223, 2224, 2225, 2226, 2227, 2228, 2229, 2230, 2231, 2232, 2233,
2234, 2235, 2236, 2237, 2238, 2239, 2240, 2241, 2242, 2243, 2244,
2245, 2246, 2247, 2248, 2249, 2250, 2251, 2252, 2253, 2254, 2255,
2256, 2257, 2258, 2259, 2260, 2271, 2272, 2273, 2274, 2275, 2276,
2277, 2278, 2279, 2280, 2281, 2282, 2283, 2284, 2285, 2286, 2287,
2288, 2289, 2290, 2291, 2292, 2293, 2294, 2295, 2296, 2297, 2298,
2299, 2300, 2301, 2302, 2303, 2304, 2305, 2306, 2307, 2308, 2309,
2310, 2311, 2312, 2313, 2314, 2315, 2316, 2317, 2318, 2319, 2320,
2321, 2322, 2323, 2324, 2325, 2326, 2327, 2328, 2329, 2330, 2331,
2332, 2333, 2334, 2335, 2336, 2337, 2338, 2339, 2340, 2341, 2342,
2343, 2344, 2345, 2346, 2347, 2348, 2349, 2350, 2351, 2352, 2353,
2354, 2355, 2356, 2357, 2358, 2359, 2360, 2361, 2362, 2363, 2364,
2365, 2366, 2367, 2368, 2369, 2370, 2371, 2372, 2373, 2374, 2375,
2376, 2377, 2378, 2379, 2380, 2381, 2382, 2383, 2384, 2385, 2386,
2387, 2388, 2389, 2390, 2391, 2392, 2393, 2394, 2395, 2396, 2397,
2398, 2399, 2400, 2401, 2402, 2403, 2404, 2405, 2406, 2407, 2408,
2409, 2410, 2411, 2412, 2413, 2414, 2415, 2416, 2417, 2418, 2419,
2420, 2421, 2422, 2423, 2424, 2425, 2426, 2427, 2428, 2429, 2430,
2431, 2432, 2433, 2434, 2435, 2436, 2437, 2438, 2439, 2440, 2441,
2442, 2443, 2444, 2445, 2446, 2447, 2448, 2449, 2450, 2451, 2452,
2453, 2454, 2455, 2456, 2457, 2458, 2459, 2460, 2461, 2462, 2463,
2464, 2465, 2466, 2467, 2468, 2469, 2470, 2471, 2472, 2473, 2474,
2475, 2476, 2477, 2478, 2479, 2480, 2481, 2482, 2483, 2484, 2485,
2486, 2487, 2488, 2489, 2490, 2491, 2492, 2493, 2494, 2495, 2496,
2497, 2498, 2499, 2500, 2501, 2502, 2503, 2504, 2505, 2506, 2507,
2508, 2509, 2510, 2511, 2512, 2513, 2514, 2515, 2516, 2517, 2518,
2519, 2520, 2521, 2522, 2523, 2524, 2525, 2526, 2527, 2528, 2529,
2530, 2531, 2532, 2533, 2534, 2535, 2536, 2537, 2538, 2539, 2540,
2541, 2542, 2543, 2544, 2545, 2546, 2547, 2548, 2549, 2550, 2551,
2552, 2553, 2554, 2555, 2556, 2557, 2558, 2559, 2560, 2561, 2562,
2563, 2564, 2565, 2566, 2567, 2568, 2569, 2570, 2571, 2572, 2573,
2574, 2575, 2576, 2577, 2578, 2579, 2580, 2581, 2582, 2583, 2584,
2585, 2586, 2587, 2588, 2589, 2590, 2591, 2592, 2593, 2594, 2595,
2596, 2597, 2598, 2599, 2600, 2601, 2602, 2603, 2604, 2605, 2606,
2607, 2608, 2609, 2610, 2611, 2612, 2613, 2614, 2615, 2616, 2617,
2618, 2619, 2620, 2621, 2622, 2623, 2624, 2625, 2626, 2627, 2628,
2629, 2630, 2631, 2632, 2633, 2634, 2635, 2636, 2637, 2638, 2639,
2640, 2641, 2642, 2643, 2644, 2645, 2646, 2647, 2648, 2649, 2650,
2651, 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660, 2661,
2662, 2663, 2664, 2665, 2666, 2667, 2668, 2669, 2670, 2671, 2672,
2673, 2674, 2675, 2676, 2677, 2678, 2679, 2680, 2681, 2682, 2683,
2684, 2685, 2686, 2687, 2688, 2689, 2690, 2691, 2692, 2693, 2694,
2695, 2696, 2697, 2698, 2699, 2700, 2701, 2702, 2703, 2704, 2705,
2706, 2707, 2708, 2709, 2710, 2711, 2712, 2713, 2714, 2715, 2716,
2717, 2718, 2719, 2720, 2721, 2722, 2723, 2724, 2725, 2726, 2727,
2728, 2729, 2730, 2731, 2732, 2733, 2734, 2735, 2736, 2737, 2738,
2739, 2740, 2741, 2742, 2743, 2744, 2745, 2746, 2747, 2748, 2749,
2750, 2751, 2752, 2753, 2754, 2755, 2756, 2757, 2758, 2759, 2760,
2761, 2762, 2763, 2764, 2765, 2766, 2767, 2768, 2769, 2770, 2771,
2772, 2773, 2774, 2775, 2776, 2777, 2778, 2779, 2780, 2781, 2782,
2783, 2784, 2785, 2786, 2787, 2788, 2789, 2790, 2791, 2792, 2793,
2794, 2795, 2796, 2797, 2798, 2799, 2800, 2801, 2802, 2803, 2804,
2805, 2806, 2807, 2808, 2809, 2810, 2811, 2812, 2813, 2814, 2815,
2816, 2817, 2818, 2819, 2820, 2821, 2822, 2823, 2824, 2825, 2826,
2827, 2828, 2829, 2830, 2831, 2832, 2833, 2834, 2835, 2836, 2837,
2838, 2839, 2840, 2841, 2842, 2843, 2844, 2845, 2846, 2847,
2848,
2849, 2850, 2851, 2852, 2853, 2854, 2855, 2856, 2857, 2858, 2859,
2860, 2861, 2862, 2863, 2864, 2865, 2866, 2867, 2868, 2869, 2870,
2871, 2872, 2873, 2874, 2875, 2876, 2877, 2878, 2879, 2880, 2881,
2882, 2883, 2884, 2885, 2886, 2887, 2888, 2889, 2890, 2891, 2892,
2893, 2894, 2895, 2896, 2897, 2898, 2899, 2900, 2901, 2902, 2903,
2904, 2905, 2906, 2907, 2908, 2909, 2910, 2911, 2912, 2913, 2914,
2915, 2916, 2917, 2918, 2919, 2920, 2921, 2922, 2923, 2924, 2925,
2926, 2927, 2928, 2929, 2930, 2931, 2932, 2933, 2934, 2935, 2936,
2937, 2938, 2939, 2940, 2941, 2942, 2943, 2944, 2945, 2946, 2947,
2948, 2949, 2950, 2951, 2952, 2953, 2954, 2955, 2956, 2957, 2958,
2959, 2960, 2961, 2962, 2963, 2964, 2965, 2966, 2967, 2968, 2969,
2970, 2971, 2972, 2973, 2974, 2975, 2976, 2977, 2978, 2979, 2980,
2981, 2982, 2983, 2984, 2985, 2986, 2987, 2988, 2989, 2990, 2991,
2992, 2993, 2994, 2995, 2996, 2997, 2998, 2999, 3000, 3001, 3002,
3003, 3004, 3005, 3006, 3007, 3008, 3009, 3010, 3011, 3012, 3013,
3014, 3015, 3016, 3017, 3018, 3019, 3020, 3021, 3022, 3023, 3024,
3025, 3026, 3027, 3028, 3029, 3030, 3031, 3032, 3033, 3034, 3035,
3036, 3037, 3038, 3039, 3040, 3042, and 3043 in SEQ ID NO: 30.
6. (canceled)
7. (canceled)
8. (canceled)
9. (canceled)
10. (canceled)
11. (canceled)
12. (canceled)
13. (canceled)
14. (canceled)
15. (canceled)
16. (canceled)
17. (canceled)
18. (canceled)
19. (canceled)
20. (canceled)
21. (canceled)
22. (canceled)
23. (canceled)
24. (canceled)
25. (canceled)
26. (canceled)
27. (canceled)
28. (canceled)
29. (canceled)
30. (canceled)
31. (canceled)
32. (canceled)
33. (canceled)
34. The polypeptide according to claim 1, which is fused or
conjugated to an immunogenic carrier molecule.
35. The polypeptide according to claim 34, wherein the immunogenic
carrier molecule is a polypeptide that induces T-helper lymphocyte
responses in a majority of humans, such as immunogenic carrier
proteins selected from the group consisting of keyhole limpet
hemocyanin or a fragment thereof, tetanus toxoid or a fragment
thereof, dipththeria toxoid or a fragment thereof.
36. The polypeptide according to claim 1, which is capable of
inducing a protective adaptive immune response against the
polypeptide in a mammal against infection with A. baumanii.
37. (canceled)
38. (canceled)
39. An isolated nucleic acid fragment, which comprises a nucleotide
sequence encoding a polypeptide according to claim 1.
40. The nucleic acid fragment according to claim 39, which is a DNA
or an RNA fragment.
41. (canceled)
42. (canceled)
43. (canceled)
44. A vector comprising the nucleic acid according to claim 39.
45. The vector according to claim 44, which comprises in operable
linkage and in the 5'-3' direction, an expression control region
comprising an enhancer/promoter for driving expression of the
nucleic acid fragment defined in claim 39, optionally a signal
peptide coding sequence, a nucleotide sequence defined in claim 39,
and optionally a terminator.
46. (canceled)
47. (canceled)
48. (canceled)
49. The vector according to claim 44, which is incapable of being
integrated into the genome of a mammalian host cell.
50. The vector according to claim 44, which is selected from the
group consisting of a virus, an attenuated virus, a bacteriophage,
a plasmid, a minichromosome, and a cosmid.
51. A cell which is transformed so as to carry the vector according
to claim 44.
52. (canceled)
53. (canceled)
54. (canceled)
55. (canceled)
56. (canceled)
57. The transformed cell according to claim 51, which secretes or
carries on its surface the polypeptide according to claim 1.
58. (canceled)
59. (canceled)
60. A pharmaceutical composition comprising a polypeptide according
to claim 1, a nucleic acid fragment according to claim 39, a vector
according to claim 44, or a cell according to claim 51, and a
pharmaceutically acceptable carrier, vehicle or diluent.
61. The pharmaceutical composition according to claim 60, which
further comprises an immunological adjuvant.
62. The pharmaceutical composition according to claim 61, wherein
the adjuvant is an aluminium based adjuvant.
63. A method for inducing protective immunity in an animal by
administering at least once an immunogenically effective amount of
a polypeptide according to claim 1, a nucleic acid fragment
according to claim 39, a vector according to claim 44, a cell
according to claim 51, or a pharmaceutical composition according to
claim 60 so as to induce protective adaptive immunity against A.
baumannii in the animal.
64. (canceled)
65. The method according to claim 63, wherein the animal receives a
priming administration and one or more booster administrations.
66. The method according to claim 63, wherein the animal is a human
being.
67. (canceled)
68. The method according to claim 63, wherein the protective
immunity is effective in reducing the risk of attracting infection
with A. baumannii or is effective in treating or ameliorating
infection with A. baumannii.
69. (canceled)
70. (canceled)
71. (canceled)
72. (canceled)
73. (canceled)
74. (canceled)
75. (canceled)
76. (canceled)
77. (canceled)
78. (canceled)
79. (canceled)
80. (canceled)
81. (canceled)
82. (canceled)
83. (canceled)
84. (canceled)
85. (canceled)
86. (canceled)
87. (canceled)
88. (canceled)
89. (canceled)
90. (canceled)
91. The polypeptide according to claim 36, wherein said mammal is a
human being.
92. The vector according to claim 44, wherein said vector is an
expression vector.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to the field of antimicrobial
prophylaxis and therapy. In particular the present invention
relates to novel proteins and polynucleotides derived from
Acinetobacter baumannii. The invention further relates to vectors
comprising the polynucleotides, transformed host organisms
expressing the polynucleotides, antibodies (mono- or polyclonal)
specific for the polypeptides as well as diagnostic, prophylactic
and therapeutic uses and methods. Finally, also methods of
preparation are part of the invention.
BACKGROUND OF THE INVENTION
[0002] Antibiotic resistance is recognized as one of the greatest
threats to human health on the planet (2009; Choffnes et al.,
Antibiotic Resistance: Implications for Global Health and Novel
Intervention Strategies, The National Academic Press, Washington,
D.C., (2010); Smolinski et al., Microbial Threats to Health:
Emergence, Detection, and Response, The Institute of Medicine,
Washington D.C., (2003); Spellberg et al., Clin Infect Dis
52(55):397-428 (2011); Spellberg et al., Clin Infect Dis 46:155-164
(2008); Walker et al., Science 325-1345-1346 (2009). In the last
decade, Acinetobacter baumannii has emerged as one of the most
common and highly antibiotic-resistant pathogens in the United
States (US) and throughout the world (Doi et al., Emerg Infect Dis
15:980-982 (2009); Higgins et al., J Antimicrob Chemother
65-233-238 (2010); Perez et al., Antimicrob Agents Chemother
51:3471-3484 (2007). Indeed, 50-70% of A. baumannii clinical
isolates are now extensively drug resistant (XDR; i.e. resistant to
carbapenems and all other antibiotics except colistin or
tigecycline), reflecting a >15-fold increase in just the past 10
years (Dizbay et al., Scand J Infect Dis (2010); Hidron et al.,
Infect Control Hosp Epidemiol 29:996-1011 (2008); Hoffmann et al.,
Infect Control Hosp Epidemiol 31:196-197 (2010); Kallen et al.,
Infect Control Hosp Epidemiol 31:528-531 (2010); Lautenbach et al.,
Infect Control Hosp Epidemolo 30:1186-1192 (2009); Mera et al.,
Drug Resist 16:209-215 (2010); Perez et al., Am J Infect Control
38:63-65 (2010); Rosenthal et al., Am J Infect Control 38:95-104
e102 (2010). Infections caused by carbapenem-resistant, XDR A.
baumannii are associated with prolonged hospitalization, tremendous
health care costs, and high rates of death despite treatment (Doi
et al., Emerg Infect Dis 15:980-982 (2009); Falagas et al., Int J
Antimicrob Agents 32:450-454 (2008); Gordon and Wareham, J
Antimicrob Chemother 63:775-780 (2009); Lautenbach et al., Infect
Control Hosp Epidemiol 30:1186-1192 (2009); Metan et al., Eur J
Intern Med 20:540-544 (2009); Park et al., Diagn Microbiol Infect
Dis 64:43-51 (2009); Perez et al., Am J Infect Control 38:63-65
(2007); Sunenshine et al., Emerg Infect Dis 13:97-103 (2007).
Indeed, bloodstream infections caused by XDR A. baumannii cause
>50-60% mortality rates despite antibiotic therapy (Gordon and
Wareham, J Antimicrob Chemother 63:775-780 (2009); Metan et al.,
Eur J Intern Med 20:540-544 (2009); Munoz-Price et al., Infect
Control Hosp Epidemiol 1(10):1057-62 (2010); Park et al., Diagn
Microbiol Infect Dis 64:43-51 (2009); Tseng et al., Diagn Microbiol
Infect Dis 59:181-190 (2007). A major reason for these high
mortality rates is that XDR A. baumannii infections are treatable
only with suboptimal second-line antibacterial agents, such as
tigecycline and colistin. Even more concerning is the increasing
resistance of A. baumannii to both colistin and tigecycline (Adams
et al., Antimicrob Agents Chemother 53:3628-3634 (2009); Doi et
al., Emerg Infect Dis 15:980-982 (2009); Falagas et al., Int J
Antimicrob Agents 32:450-454 (2008); Hernan et al., Diagn Microbiol
Infect Dis 65:188-191 (2009); Livermore et al., Int J Antimicrob
Agents 35:19-24 (2010); Park et al., Diagn Microbiol Infect Dis
64:43-51 (2009); Valencia et al., Infect Control Hosp Epidemiol
30:257-263 (2009); Wang and Dowzicky, Diagn Microbiol Infect Dis
68:73-79 (2010). Such pan-drug resistant (PDR) A. baumannii
infections are resistant to every FDA approved antibiotic, and are
hence untreatable.
[0003] New methods to prevent and treat A. baumannii infections are
critically needed, especially since no new drugs to treat these
infections are in the antibacterial pipeline for the coming decade
(Boucher et al., Clin Infect Dis 48:1-12 (2009); Spellberg et al.,
Clin Infect Dis 46:155-164 (2008). Since risk factors for A.
baumannii infections are understood (Beavers et al., 2009; Caricato
et al., Intensive Care Med 35:1964-1969 (2009); D'Agata et al.,
Infect Control Hosp Epidemiol 21:588-591 (2000); Furniss et al., J
Burn Care Rehabil 26:405-408 (2005); Metan et al., Eur J Intern Med
20:540-544 (2009); Zakuan et al., Trop Biomed 26:123-129 (2009),
vaccination of acutely at-risk patients is a promising method to
prevent such infections, and antibody-based immunotherapy has
promise to improve outcomes from infection.
[0004] The first full-genome sequence of A. baumannii was performed
in 2007 (strain ATCC 17978) with a chromosome of 3976747 base
pairs
[0005] Vaccination is considered to be a very effective method of
preventing infectious diseases in human and veterinary health care.
Vaccination is the administration of immunogenically effective
amounts of antigenic material (the vaccine) to produce immunity to
a disease/disease-causing pathogenic agent. Vaccines have
contributed to the eradication of smallpox, the near eradication of
polio, and the control of a variety of diseases, including rubella,
measles, mumps, chickenpox, typhoid fever.
[0006] Before "the genomic era", vaccines were based on killed or
live attenuated, microorganisms, or parts purified from them.
Subunit vaccines are considered as a modern upgrade of these types
of vaccine, as the subunit vaccines contain one or more protective
antigens, which are more or less the weak spot of the pathogen.
Hence, in order to develop subunit vaccines, it is critical to
identify the proteins, which are important for inducing protection
and to eliminate others.
[0007] An antigen is said to be protective if it is able to induce
protection from subsequent challenge by a disease-causing
infectious agent in an appropriate animal model following
immunization.
[0008] The empirical approach to subunit vaccine development, which
includes several steps, begins with pathogen cultivation, followed
by purification into components, and then testing of antigens for
protection. Apart from being time and labour consuming, this
approach has several limitations that can lead to failure. It is
not possible to develop vaccines using this approach for
microorganisms, which cannot easily be cultured and only allows for
the identification of the antigens, which can be obtained in
sufficient quantities. The empirical approach has a tendency to
focus on the most abundant proteins, which in some cases are not
immuno-protective. In other cases, the antigen expressed during in
vivo infection is not expressed during in vitro cultivation.
Furthermore, antigen discovery by use of the empirical approach
demands an extreme amount of proteins in order to discover the
protective antigens, which are like finding needles in the
haystack. This renders it a very expensive approach, and it limits
the vaccine development around diseases, which is caused by
pathogens with a large genome or disease areas, which perform badly
in a cost-effective perspective.
OBJECT OF THE INVENTION
[0009] It is an object of embodiments of the invention to provide
A. baumannii derived antigenic polypeptides that may serve as
constituents in vaccines against A. baumannii infections and in
diagnosis of A. baumannii infections. It is also an object to
provide nucleic acids, vectors, transformed cells, vaccine
compositions, and other useful means for molecular cloning as well
as for therapy and diagnosis with relevance for A. baumannii.
SUMMARY OF THE INVENTION
[0010] It has been found by the present inventor(s) that A.
baumannii, expresses a number of hitherto unknown putatively
surface exposed proteins which are candidates as vaccine targets as
well as candidates as immunizing agents for preparation of
antibodies that target A. baumannii.
[0011] So, in a first aspect the present invention relates to a
polypeptide comprising
a) an amino acid sequence selected from the group consisting of any
one of SEQ ID NOs: 1-30, or b) an amino acid sequence consisting of
at least 5 contiguous amino acid residues from any one of SEQ ID
NOs: 1-30, or c) an amino acid sequence having a sequence identity
of at least 60% with the amino acid sequence of a), d) an amino
acid sequence having a sequence identity of at least 60% with the
amino acid sequence of b), or e) an assembly of amino acids derived
from any one of SEQ ID NOs: 1-30 which has essentially the same 3D
conformation as in the protein from which said assembly is derived
so as to constitute a B-cell epitope, said polypeptide being
antigenic in a mammal.
[0012] In another aspect, the invention relates to an isolated
nucleic acid fragment, which comprises
i) a nucleotide sequence encoding a polypeptide of the invention,
or ii) a nucleotide sequence consisting of any one of SEQ ID NOs:
31-60. iii) a nucleotide sequence consisting of at least 10
consecutive nucleotides in any one of SEQ ID NOs: 31-60, iv) a
nucleotide sequence having a sequence identity of at least 60% with
the nucleotide sequence in i) or ii), v) a nucleotide sequence
having a sequence identity of at least 60% with the nucleotide
sequence in iii), vi) a nucleotide sequence complementary to the
nucleotide sequence in i)-v), or vii) a nucleotide sequence which
hybridizes under stringent conditions with the nucleotide sequence
in i)-vi).
[0013] In a third aspect, the invention relates to a vector
comprising the nucleic acid of the invention, such as a cloning
vector or an expression vector.
[0014] In fourth aspect, the invention relates to a cell which is
transformed so as to carry the vector of the invention.
[0015] In a fifth aspect, the invention relates to a pharmaceutical
composition comprising a polypeptide of the invention, a nucleic
acid fragment of the invention, a vector of the invention, or a
transformed cell of the invention, and a pharmaceutically
acceptable carrier, vehicle or diluent.
[0016] In a sixth aspect, the invention relates to a method for
inducing immunity in an animal by administering at least once an
immunogenically effective amount of a polypeptide of the invention,
a nucleic acid fragment of the invention, a vector of the
invention, a transformed cell of the invention, or a pharmaceutical
composition of the fifth aspect of the invention so as to induce
adaptive immunity against A. baumannii in humans or animals.
[0017] In a seventh and eighth aspect, the invention relates to 1)
a polyclonal antibody in which the antibodies specifically bind to
at least one polypeptide of the invention, and which is essentially
free from antibodies binding specifically to other A. baumannii
polypeptides, and to 2) an isolated monoclonal antibody or antibody
analogue which binds specifically to a polypeptide of the
invention. In a related ninth aspect, the invention relates to a
pharmaceutical composition comprising such a polyclonal or
monoclona antibody and a pharmaceutically acceptable carrier,
vehicle or diluent.
[0018] In a 10.sup.th aspect, the invention relates to a method for
prophylaxis, treatment or amelioration of infection with A.
baumannii, comprising administering a therapeutically effective
amount of an antibody of the 7.sup.th or 8.sup.th aspect of the
invention or a pharmaceutical composition of the eighth aspect to
an individual in need thereof.
[0019] In an 11.sup.th aspect, the invention relates to a method
for determining, quantitatively or qualitatively, the presence of
A. baumannii, in particular the presence of multi-resistant A.
baumannii, in a sample, the method comprising contacting the sample
with an antibody of aspects 8 or 9 of the invention and detecting
the presence of antibody bound to material in the sample.
[0020] In an 12.sup.th aspect of the invention is provided a method
for determining, quantitatively or qualitatively, the presence of
antibodies specific for A. baumannii, in particular the presence of
antibodies specific for multi-resistant A. baumannii, in a sample,
the method comprising contacting the sample with a polypeptide of
the invention and detecting the presence of antibody that
specifically bind said polypeptide.
[0021] In a 13.sup.th aspect, the invention relates to a method for
determining, quantitatively or qualitatively, the presence of a
nucleic acid characteristic of A. baumannii, in particular the
presence of a nucleic acid characteristic of multi-resistant A.
baumannii, in a sample, the method comprising contacting the sample
with a nucleic acid fragment of the invention and detecting the
presence of nucleic acid in the sample that hybridizes to said
nucleic acid fragment.
[0022] In a 14.sup.th aspect, the invention relates to a method for
the preparation of the polypeptide of the invention, comprising
[0023] culturing a transformed cell of the present invention, which
is capable of expressing the nucleic acid of the invention, under
conditions that facilitate that the transformed cell expresses the
nucleic acid fragment of the invention, which encodes a polypeptide
of the invention, and subsequently recovering said polypeptide, or
[0024] preparing said polypeptide by means of solid or liquid phase
peptide synthesis.
[0025] In a 15.sup.th aspect, the invention relates to a method for
determining whether a substance, such as an antibody, is
potentially useful for treating infection with A. baumannii, the
method comprising contacting the polypeptide of the invention with
the substance and subsequently establishing whether the substance
has at least one of the following characteristics:
1) the ability to bind specifically to said polypeptide, 2) the
ability to compeed with said polypeptide for specific binding to a
ligand/receptor, and 3) the ability to specifically inactivate said
polypeptide.
[0026] Finally, in a 16.sup.th aspect, the invention relates to a
method for determining whether a substance, such as a nucleic acid,
is potentially useful for treating infection with A. baumannii, the
method comprising contacting the substance with the nucleic acid
fragment of claim of the invention and subsequently establishing
whether the substance has either the ability to
1) bind specifically to the nucleic acid fragment, or 2) bind
specifically to a nucleic acid that hybridizes specifically with
the nucleic acid fragment.
DETAILED DISCLOSURE OF THE INVENTION
[0027] Definitions
[0028] The term "polypeptide" is in the present context intended to
mean both short peptides of from 2 to 10 amino acid residues,
oligopeptides of from 11 to 100 amino acid residues, and
polypeptides of more than 100 amino acid residues. Further-more,
the term is also intended to include proteins, i.e. functional
biomolecules comprising at least one polypeptide; when comprising
at least two polypeptides, these may form complexes, be covalently
linked, or may be non-covalently linked. The polypeptide (s) in a
protein can be glycosylated and/or lipidated and/or comprise
prosthetic groups.
[0029] The term "subsequence" means any consecutive stretch of at
least 3 amino acids or, when relevant, of at least 3 nucleotides,
derived directly from a naturally occurring amino acid sequence or
nucleic acid sequence, respectively
[0030] The term "amino acid sequence" s the order in which amino
acid residues, connected by peptide bonds, lie in the chain in
peptides and proteins.
[0031] The term "adjuvant" has its usual meaning in the art of
vaccine technology, i.e. a substance or a composition of matter
which is 1) not in itself capable of mounting a specific immune
response against the immunogen of the vaccine, but which is 2)
nevertheless capable of enhancing the immune response against the
immunogen. Or, in other words, vaccination with the adjuvant alone
does not provide an immune response against the immunogen,
vaccination with the immunogen may or may not give rise to an
immune response against the immunogen, but the combined vaccination
with immunogen and adjuvant induces an immune response against the
immunogen which is stronger than that induced by the immunogen
alone.
[0032] "Sequence identity" is in the context of the present
invention determined by comparing 2 optimally aligned sequences of
equal length (e.g. DNA, RNA or amino acid) according to the
following formula: (N.sub.ref-N.sub.dif)100/N.sub.ref, wherein
N.sub.ref is the number of residues in one of the 2 sequences and
N.sub.dif is the number of residues which are non-identical in the
two sequences when they are aligned over their entire lengths and
in the same direction. So, two sequences 5'-ATTCGGAACC-3' and
5'-ATACGGGACC-3' will provide the sequence identity 80%
(N.sub.ref=10 and N.sub.dif=2).
[0033] An "assembly of amino acids" means two or more amino acids
bound together by physical or chemical means.
[0034] The "3D conformation" is the 3 dimensional structure of a
biomolecule such as a protein. In monomeric polypeptides/proteins,
the 3D conformation is also termed "the tertiary structure" and
denotes the relative locations in 3 dimensional space of the amino
acid residues forming the polypeptide.
[0035] "An immunogenic carrier" is a molecule or moiety to which an
immunogen or a hapten can be coupled in order to enhance or enable
the elicitation of an immune response against the immunogen/hapten.
Immunogenic carriers are in classical cases relatively large
molecules (such as tetanus toxoid, KLH, diphtheria toxoid etc.)
which can be fused or conjugated to an immunogen/hapten, which is
not sufficiently immunogenic in its own right--typically, the
immunogenic carrier is capable of eliciting a strong T-helper
lymphocyte response against the combined substance constituted by
the immunogen and the immunogenic carrier, and this in turn
provides for improved responses against the immungon by
B-lymphocytes and cytotoxic lymphocytes. More recently, the large
carrier molecules have to a certain extent been substituted by
so-called promiscuous T-helper epitopes, i.e. shorter peptides that
are recognized by a large fraction of HLA haplotypes in a
population, and which elicit T-helper lymphocyte responses.
[0036] A "T-helper lymphocyte response" is an immune response
elicited on the basis of a peptide, which is able to bind to an MHC
class II molecule (e.g. an HLA class II molecule) in an
antigen-presenting cell and which stimulates T-helper lymphocytes
in an animal species as a consequence of T-cell receptor
recognition of the complex between the peptide and the MHC Class II
molecule prese
[0037] An "immunogen" is a substance of matter which is capable of
inducing an adaptive immune response in a host, whose immune system
is confronted with the immunogen. As such, immunogens are a subset
of the larger genus "antigens", which are substances that can be
recognized specifically by the immune system (e.g. when bound by
antibodies or, alternatively, when fragments of the are antigens
bound to MHC molecules are being recognized by T-cell receptors)
but which are not necessarily capable of inducing immunity--an
antigen is, however, always capable of eliciting immunity, meaning
that a host that has an established memory immunity against the
antigen will mount a specific immune response against the
antigen.
[0038] A "hapten" is a small molecule, which can neither induce or
elicit an immune response, but if conjugated to an immunogenic
carrier, antibodies or TCRs that recognize the hapten can be
induced upon confrontation of the immune system with the hapten
carrier conjugate.
[0039] An "adaptive immune response" is an immune response in
response to confrontation with an antigen or immunogen, where the
immune response is specific for antigene determinants of the
antigen/immunogen--examples of adaptive immune responses are
induction of antigen specific antibody production or antigen
specific induction/activation of T helper lymphocytes or cytotoxic
lymphocytes.
[0040] A "protective, adaptive immune response" is an
antigen-specific immune response induced in a subject as a reaction
to immunization (artificial or natural) with an antigen, where the
immune response is capable of protecting the subject against
subsequent challenges with the antigen or a pathology-related agent
that includes the antigen. Typically, prophylactic vaccination aims
at establishing a protective adaptive immune response against one
or several pathogens.
[0041] "Stimulation of the immune system" means that a substance or
composition of matter exhibits a general, non-specific
immunostimulatory effect. A number of adjuvants and putative
adjuvants (such as certain cytokines) share the ability to
stimulate the immune system. The result of using an
immunostimulating agent is an increased "alertness" of the immune
system meaning that simultaneous or subsequent immunization with an
immunogen induces a significantly more effective immune response
compared to isolated use of the immunogen.
[0042] Hybridization under "stringent conditions" is herein defined
as hybridization performed under conditions by which a probe will
hybridize to its target sequence, to a detectably greater degree
than to other sequences. Stringent conditions are
target-sequence-dependent and will differ depending on the
structure of the polynucleotide. By controlling the stringency of
the hybridization and/or washing conditions, target sequences can
be identified which are 100% complementary to a probe (homologous
probing). Alternatively, stringency conditions can be adjusted to
allow some mismatching in sequences so that lower degrees of
similarity are detected (heterologous probing). Specificity is
typically the function of post-hybridization washes, the critical
factors being the ionic strength and temperature of the final wash
solution. Generally, stringent wash temperature conditions are
selected to be about 5.degree. C. to about 2.degree. C. lower than
the melting point (Tm) for the specific sequence at a defined ionic
strength and pH. The melting point, or denaturation, of DNA occurs
over a narrow temperature range and represents the disruption of
the double helix into its complementary single strands. The process
is described by the temperature of the midpoint of transition, Tm,
which is also called the melting temperature. Formulas are
available in the art for the determination of melting
temperatures.
[0043] The term "animal" is in the present context in general
intended to denote an animal species (preferably mammalian), such
as Homo sapiens, Canis domesticus, etc. and not just one single
animal. However, the term also denotes a population of such an
animal species, since it is important that the individuals
immunized according to the method of the invention substantially
all will mount an immune response against the immunogen of the
present invention.
[0044] As used herein, the term "antibody" refers to a polypeptide
or group of polypeptides composed of at least one antibody
combining site. An "antibody combining site" is the
three-dimensional binding space with an internal surface shape and
charge distribution complementary to the features of an epitope of
an antigen, which allows a binding of the antibody with the
antigen. "Antibody" includes, for example, vertebrate antibodies,
hybrid antibodies, chimeric antibodies, humanised antibodies,
altered antibodies, univalent antibodies, Fab proteins, and single
domain antibodies.
[0045] "Specific binding" denotes binding between two substances
which goes beyond binding of either substance to randomly chosen
substances and also goes beyond simple association between
substances that tend to aggregate because they share the same
overall hydrophobicity or hydrophilicity. As such, specific binding
usually involves a combination of electrostatic and other
interactions between two conformationally complementary areas on
the two substances, meaning that the substances can "recognize"
each other in a complex mixture.
[0046] The term "vector" is used to refer to a carrier nucleic acid
molecule into which a heterologous nucleic acid sequence can be
inserted for introduction into a cell where it can be replicated
and expressed. The term further denotes certain biological vehicles
useful for the same purpose, e.g. viral vectors and phage--both
these infectious agents are capable of introducing a heterelogous
nucleic acid sequence
[0047] The term "expression vector" refers to a vector containing a
nucleic acid sequence coding for at least part of a gene product
capable of being transcribed. In some cases, when the transcription
product is an mRNA molecule, this is in trun translated into a
protein, polypeptide, or peptide.
Specific Embodiments of the Invention
The Polypeptides of the Invention
[0048] In some embodiments the at least 5 contiguous amino acids
referred to in option b) in the definition of the first aspect of
the invention may preferably constitute at least or exactly or at
most 6, such as at least or exactly or at most 7, at least or
exactly or at most 8, at least or exactly or at most 9, at least or
exactly or at most 10, at least or exactly or at most 11, at least
or exactly or at most 12, at least or exactly or at most 13, at
least or exactly or at most 14, at least or exactly or at most 15,
at least or exactly or at most 16, at least or exactly or at most
17, at least or exactly or at most 18, at least or exactly or at
most 19, at least or exactly or at most 20, at least or exactly or
at most 21, at least or exactly or at most 22, at least or exactly
or at most 23, at least or exactly or at most 24, at least or
exactly or at most 25, at least or exactly or at most 26, at least
or exactly or at most 27 at least or exactly or at most 28, at
least or exactly or at most 29, at least or exactly or at most 30,
at least or exactly or at most 31, at least or exactly or at most
32, at least or exactly or at most 33, at least or exactly or at
most 34, at least or exactly or at most 35 and at least or exactly
or at most 36, at least or exactly or at most 37, at least or
exactly or at most 38, at least or exactly or at most 39, at least
or exactly or at most 40, at least or exactly or at most 41, at
least or exactly or at most 42, at least or exactly or at most 43,
at least or exactly or at most 44, at least or exactly or at most
45, at least or exactly or at most 46, at least or exactly or at
most 47, at least or exactly or at most 48, at least or exactly or
at most 49, at least or exactly or at most 50, at least or exactly
or at most 51, at least or exactly or at most 52, at least or
exactly or at most 53, at least or exactly or at most 54, at least
or exactly or at most 55 and at least or exactly or at most 56, at
least or exactly or at most 57, at least or exactly or at most 58,
at least or exactly or at most 59, or at least or exactly or at
most 60 contiguous amino acid residues.
[0049] The number may, where applicable, be higher. Another way to
phrase this is that for each of SEQ ID NOs: 1-30, the number of the
contiguous amino acid residues is at least N-n, where N is the
length of the sequence ID in question and n is any integer between
6 and N-1; that is, the at least 5 contiguous amino acids can be at
least any number between 5 and the length of the reference sequence
minus one, in increments of one. Consequently:
[0050] Insofar as embodiment b relates to SEQ ID NO: 2-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 61, at least or exactly
or at most 62, at least or exactly or at most 63, at least or
exactly or at most 64, at least or exactly or at most 65, at least
or exactly or at most 66 contiguous amino acid residues.
[0051] Insofar as embodiment b relates to SEQ ID NO: 4-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 67, at least or exactly
or at most 68, at least or exactly or at most 69, at least or
exactly or at most 70, at least or exactly or at most 71, at least
or exactly or at most 72, at least or exactly or at most 73
contiguous amino acid residues.
[0052] Insofar as embodiment b relates to SEQ ID NO: 5-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 74, at least or exactly
or at most 75, at least or exactly or at most 76, at least or
exactly or at most 77, at least or exactly or at most 78, at least
or exactly or at most 79, at least or exactly or at most 80, at
least or exactly or at most 81, at least or exactly or at most 82,
at least or exactly or at most 83, at least or exactly or at most
84, at least or exactly or at most 85, at least or exactly or at
most 86, at least or exactly or at most 87, at least or exactly or
at most 88, at least or exactly or at most 89, at least or exactly
or at most 90, at least or exactly or at most 91, at least or
exactly or at most 92, at least or exactly or at most 93, at least
or exactly or at most 94, at least or exactly or at most 95, at
least or exactly or at most 96, at least or exactly or at most 97,
at least or exactly or at most 98, at least or exactly or at most
99, at least or exactly or at most 100, at least or exactly or at
most 101, at least or exactly or at most 102, at least or exactly
or at most 103, at least or exactly or at most 104, at least or
exactly or at most 105, at least or exactly or at most 106, at
least or exactly or at most 107, at least or exactly or at most 108
contiguous amino acid residues.
[0053] Insofar as embodiment b relates to SEQ ID NO: 6-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 109, at least or exactly
or at most 110, at least or exactly or at most 111, at least or
exactly or at most 112, at least or exactly or at most 113, at
least or exactly or at most 114 contiguous amino acid residues.
[0054] Insofar as embodiment b relates to SEQ ID NO: 7-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 115, at least or exactly
or at most 116, at least or exactly or at most 117, at least or
exactly or at most 118, at least or exactly or at most 119, at
least or exactly or at most 120, at least or exactly or at most
121, at least or exactly or at most 122, at least or exactly or at
most 123, at least or exactly or at most 124, at least or exactly
or at most 125, at least or exactly or at most 126 contiguous amino
acid residues.
[0055] Insofar as embodiment b relates to SEQ ID NO: 8-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 127, at least or exactly
or at most 128, at least or exactly or at most 129, at least or
exactly or at most 130, at least or exactly or at most 131, at
least or exactly or at most 132, at least or exactly or at most
133, at least or exactly or at most 134, at least or exactly or at
most 135, at least or exactly or at most 136, at least or exactly
or at most 137, at least or exactly or at most 138, at least or
exactly or at most 139 contiguous amino acid residues.
[0056] Insofar as embodiment b relates to SEQ ID NO: 9-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 140, at least or exactly
or at most 141, at least or exactly or at most 142, at least or
exactly or at most 143, at least or exactly or at most 144, at
least or exactly or at most 145, at least or exactly or at most
146, at least or exactly or at most 147, at least or exactly or at
most 148, at least or exactly or at most 149, at least or exactly
or at most 150, at least or exactly or at most 151, at least or
exactly or at most 152, at least or exactly or at most 153, at
least or exactly or at most 154, at least or exactly or at most
155, at least or exactly or at most 156, at least or exactly or at
most 157, at least or exactly or at most 158, at least or exactly
or at most 159 contiguous amino acid residues.
[0057] Insofar as embodiment b relates to SEQ ID NO: 10-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 160, at least or exactly
or at most 161, at least or exactly or at most 162 contiguous amino
acid residues.
[0058] Insofar as embodiment b relates to SEQ ID NO: 11-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 163, at least or exactly
or at most 164, at least or exactly or at most 165, at least or
exactly or at most 166 contiguous amino acid residues.
[0059] Insofar as embodiment b relates to SEQ ID NO: 12-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 167, at least or exactly
or at most 168, at least or exactly or at most 169, at least or
exactly or at most 170, at least or exactly or at most 171, at
least or exactly or at most 172, at least or exactly or at most
173, at least or exactly or at most 174, at least or exactly or at
most 175, at least or exactly or at most 176, at least or exactly
or at most 177, at least or exactly or at most 178, at least or
exactly or at most 179, at least or exactly or at most 180, at
least or exactly or at most 181, at least or exactly or at most
182, at least or exactly or at most 183, at least or exactly or at
most 184, at least or exactly or at most 185, at least or exactly
or at most 186, at least or exactly or at most 187, at least or
exactly or at most 188, at least or exactly or at most 189, at
least or exactly or at most 190, at least or exactly or at most
191, at least or exactly or at most 192, at least or exactly or at
most 193, at least or exactly or at most 194, at least or exactly
or at most 195, at least or exactly or at most 196, at least or
exactly or at most 197, at least or exactly or at most 198, at
least or exactly or at most 199, at least or exactly or at most
200, at least or exactly or at most 201, at least or exactly or at
most 202, at least or exactly or at most 203, at least or exactly
or at most 204, at least or exactly or at most 205, at least or
exactly or at most 206, at least or exactly or at most 207, at
least or exactly or at most 208, at least or exactly or at most
209, at least or exactly or at most 210, at least or exactly or at
most 211, at least or exactly or at most 212, at least or exactly
or at most 213, at least or exactly or at most 214, at least or
exactly or at most 215, at least or exactly or at most 216, at
least or exactly or at most 217, at least or exactly or at most
218, at least or exactly or at most 219, at least or exactly or at
most 220, at least or exactly or at most 221, at least or exactly
or at most 222, at least or exactly or at most 223, at least or
exactly or at most 224, at least or exactly or at most 225, at
least or exactly or at most 226, at least or exactly or at most
227, at least or exactly or at most 228, at least or exactly or at
most 229, at least or exactly or at most 230 contiguous amino acid
residues.
[0060] Insofar as embodiment b relates to SEQ ID NO: 13-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 231, at least or exactly
or at most 232, at least or exactly or at most 233, at least or
exactly or at most 234, at least or exactly or at most 235, at
least or exactly or at most 236, at least or exactly or at most
237, at least or exactly or at most 238 contiguous amino acid
residues.
[0061] Insofar as embodiment b relates to SEQ ID NO: 14-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 239, at least or exactly
or at most 240, at least or exactly or at most 241, at least or
exactly or at most 242, at least or exactly or at most 243, at
least or exactly or at most 244, at least or exactly or at most
245, at least or exactly or at most 246, at least or exactly or at
most 247, at least or exactly or at most 248, at least or exactly
or at most 249, at least or exactly or at most 250, at least or
exactly or at most 251, at least or exactly or at most 252, at
least or exactly or at most 253 contiguous amino acid residues.
[0062] Insofar as embodiment b relates to SEQ ID NO: 15-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 254, at least or exactly
or at most 255, at least or exactly or at most 256, at least or
exactly or at most 257, at least or exactly or at most 258, at
least or exactly or at most 259, at least or exactly or at most
260, at least or exactly or at most 261, at least or exactly or at
most 262, at least or exactly or at most 263, at least or exactly
or at most 264, at least or exactly or at most 265, at least or
exactly or at most 266, at least or exactly or at most 267, at
least or exactly or at most 268, at least or exactly or at most
269, at least or exactly or at most 270, at least or exactly or at
most 271, at least or exactly or at most 272, at least or exactly
or at most 273, at least or exactly or at most 274, at least or
exactly or at most 275, at least or exactly or at most 276, at
least or exactly or at most 277, at least or exactly or at most
278, at least or exactly or at most 279, at least or exactly or at
most 280, at least or exactly or at most 281, at least or exactly
or at most 282, at least or exactly or at most 283, at least or
exactly or at most 284, at least or exactly or at most 285, at
least or exactly or at most 286, at least or exactly or at most
287, at least or exactly or at most 288, at least or exactly or at
most 289, at least or exactly or at most 290, at least or exactly
or at most 291, at least or exactly or at most 292, at least or
exactly or at most 293, at least or exactly or at most 294
contiguous amino acid residues.
[0063] Insofar as embodiment b relates to SEQ ID NO: 16-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 295, at least or exactly
or at most 296, at least or exactly or at most 297, at least or
exactly or at most 298, at least or exactly or at most 299, at
least or exactly or at most 300, at least or exactly or at most
301, at least or exactly or at most 302, at least or exactly or at
most 303, at least or exactly or at most 304, at least or exactly
or at most 305, at least or exactly or at most 306, at least or
exactly or at most 307, at least or exactly or at most 308, at
least or exactly or at most 309, at least or exactly or at most
310, at least or exactly or at most 311, at least or exactly or at
most 312, at least or exactly or at most 313, at least or exactly
or at most 314, at least or exactly or at most 315, at least or
exactly or at most 316, at least or exactly or at most 317, at
least or exactly or at most 318, at least or exactly or at most
319, at least or exactly or at most 320, at least or exactly or at
most 321, at least or exactly or at most 322, at least or exactly
or at most 323, at least or exactly or at most 324, at least or
exactly or at most 325, at least or exactly or at most 326, at
least or exactly or at most 327, at least or exactly or at most
328, at least or exactly or at most 329, at least or exactly or at
most 330, at least or exactly or at most 331, at least or exactly
or at most 332, at least or exactly or at most 333, at least or
exactly or at most 334, at least or exactly or at most 335, at
least or exactly or at most 336, at least or exactly or at most
337, at least or exactly or at most 338, at least or exactly or at
most 339, at least or exactly or at most 340, at least or exactly
or at most 341, at least or exactly or at most 342, at least or
exactly or at most 343, at least or exactly or at most 344, at
least or exactly or at most 345, at least or exactly or at most
346, at least or exactly or at most 347, at least or exactly or at
most 348, at least or exactly or at most 349, at least or exactly
or at most 350, at least or exactly or at most 351, at least or
exactly or at most 352, at least or exactly or at most 353, at
least or exactly or at most 354, at least or exactly or at most
355, at least or exactly or at most 356 contiguous amino acid
residues.
[0064] Insofar as embodiment b relates to SEQ ID NO: 17-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 357, at least or exactly
or at most 358, at least or exactly or at most 359, at least or
exactly or at most 360, at least or exactly or at most 361, at
least or exactly or at most 362, at least or exactly or at most
363, at least or exactly or at most 364, at least or exactly or at
most 365, at least or exactly or at most 366, at least or exactly
or at most 367 contiguous amino acid residues.
[0065] Insofar as embodiment b relates to SEQ ID NO: 18-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 368, at least or exactly
or at most 369, at least or exactly or at most 370, at least or
exactly or at most 371, at least or exactly or at most 372, at
least or exactly or at most 373, at least or exactly or at most
374, at least or exactly or at most 375, at least or exactly or at
most 376, at least or exactly or at most 377, at least or exactly
or at most 378, at least or exactly or at most 379, at least or
exactly or at most 380, at least or exactly or at most 381, at
least or exactly or at most 382, at least or exactly or at most
383, at least or exactly or at most 384, at least or exactly or at
most 385, at least or exactly or at most 386, at least or exactly
or at most 387, at least or exactly or at most 388, at least or
exactly or at most 389, at least or exactly or at most 390, at
least or exactly or at most 391, at least or exactly or at most
392, at least or exactly or at most 393, at least or exactly or at
most 394, at least or exactly or at most 395, at least or exactly
or at most 396, at least or exactly or at most 397, at least or
exactly or at most 398, at least or exactly or at most 399, at
least or exactly or at most 400, at least or exactly or at most
401, at least or exactly or at most 402, at least or exactly or at
most 403, at least or exactly or at most 404, at least or exactly
or at most 405, at least or exactly or at most 406, at least or
exactly or at most 407, at least or exactly or at most 408, at
least or exactly or at most 409, at least or exactly or at most
410, at least or exactly or at most 411, at least or exactly or at
most 412, at least or exactly or at most 413, at least or exactly
or at most 414, at least or exactly or at most 415, at least or
exactly or at most 416, at least or exactly or at most 417, at
least or exactly or at most 418, at least or exactly or at most
419, at least or exactly or at most 420 contiguous amino acid
residues.
[0066] Insofar as embodiment b relates to SEQ ID NO: 19-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 421, at least or exactly
or at most 422, at least or exactly or at most 423, at least or
exactly or at most 424, at least or exactly or at most 425, at
least or exactly or at most 426, at least or exactly or at most
427, at least or exactly or at most 428, at least or exactly or at
most 429, at least or exactly or at most 430, at least or exactly
or at most 431, at least or exactly or at most 432, at least or
exactly or at most 433, at least or exactly or at most 434, at
least or exactly or at most 435, at least or exactly or at most
436, at least or exactly or at most 437, at least or exactly or at
most 438, at least or exactly or at most 439, at least or exactly
or at most 440, at least or exactly or at most 441, at least or
exactly or at most 442, at least or exactly or at most 443, at
least or exactly or at most 444, at least or exactly or at most 445
contiguous amino acid residues.
[0067] Insofar as embodiment b relates to SEQ ID NO: 20-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 446, at least or exactly
or at most 447, at least or exactly or at most 448, at least or
exactly or at most 449, at least or exactly or at most 450, at
least or exactly or at most 451, at least or exactly or at most
452, at least or exactly or at most 453, at least or exactly or at
most 454, at least or exactly or at most 455, at least or exactly
or at most 456, at least or exactly or at most 457, at least or
exactly or at most 458, at least or exactly or at most 459, at
least or exactly or at most 460, at least or exactly or at most
461, at least or exactly or at most 462, at least or exactly or at
most 463, at least or exactly or at most 464, at least or exactly
or at most 465, at least or exactly or at most 466, at least or
exactly or at most 467, at least or exactly or at most 468, at
least or exactly or at most 469, at least or exactly or at most
470, at least or exactly or at most 471, at least or exactly or at
most 472, at least or exactly or at most 473, at least or exactly
or at most 474, at least or exactly or at most 475, at least or
exactly or at most 476, at least or exactly or at most 477, at
least or exactly or at most 478, at least or exactly or at most
479, at least or exactly or at most 480, at least or exactly or at
most 481, at least or exactly or at most 482, at least or exactly
or at most 483, at least or exactly or at most 484, at least or
exactly or at most 485, at least or exactly or at most 486, at
least or exactly or at most 487, at least or exactly or at most
488, at least or exactly or at most 489, at least or exactly or at
most 490, at least or exactly or at most 491, at least or exactly
or at most 492, at least or exactly or at most 493, at least or
exactly or at most 494, at least or exactly or at most 495, at
least or exactly or at most 496, at least or exactly or at most
497, at least or exactly or at most 498, at least or exactly or at
most 499, at least or exactly or at most 500, at least or exactly
or at most 501, at least or exactly or at most 502, at least or
exactly or at most 503, at least or exactly or at most 504, at
least or exactly or at most 505, at least or exactly or at most
506, at least or exactly or at most 507, at least or exactly or at
most 508, at least or exactly or at most 509, at least or exactly
or at most 510, at least or exactly or at most 511, at least or
exactly or at most 512, at least or exactly or at most 513, at
least or exactly or at most 514, at least or exactly or at most
515, at least or exactly or at most 516, at least or exactly or at
most 517, at least or exactly or at most 518, at least or exactly
or at most 519, at least or exactly or at most 520, at least or
exactly or at most 521, at least or exactly or at most 522, at
least or exactly or at most 523, at least or exactly or at most
524, at least or exactly or at most 525, at least or exactly or at
most 526, at least or exactly or at most 527, at least or exactly
or at most 528, at least or exactly or at most 529, at least or
exactly or at most 530, at least or exactly or at most 531, at
least or exactly or at most 532, at least or exactly or at most
533, at least or exactly or at most 534, at least or exactly or at
most 535, at least or exactly or at most 536, at least or exactly
or at most 537, at least or exactly or at most 538, at least or
exactly or at most 539, at least or exactly or at most 540, at
least or exactly or at most 541, at least or exactly or at most
542, at least or exactly or at most 543, at least or exactly or at
most 544, at least or exactly or at most 545, at least or exactly
or at most 546, at least or exactly or at most 547, at least or
exactly or at most 548, at least or exactly or at most 549, at
least or exactly or at most 550, at least or exactly or at most
551, at least or exactly or at most 552, at least or exactly or at
most 553, at least or exactly or at most 554, at least or exactly
or at most 555, at least or exactly or at most 556, at least or
exactly or at most 557, at least or exactly or at most 558, at
least or exactly or at most 559, at least or exactly or at most
560, at least or exactly or at most 561, at least or exactly or at
most 562, at least or exactly or at most 563, at least or exactly
or at most 564, at least or exactly or at most 565, at least or
exactly or at most 566, at least or exactly or at most 567, at
least or exactly or at most 568, at least or exactly or at most
569, at least or exactly or at most 570, at least or exactly or at
most 571, at least or exactly or at most 572, at least or exactly
or at most 573, at least or exactly or at most 574, at least or
exactly or at most 575, at least or exactly or at most 576, at
least or exactly or at most 577, at least or exactly or at most
578, at least or exactly or at most 579, at least or exactly or at
most 580, at least or exactly or at most 581, at least or exactly
or at most 582, at least or exactly or at most 583, at least or
exactly or at most 584, at least or exactly or at most 585, at
least or exactly or at most 586, at least or exactly or at most
587, at least or exactly or at most 588, at least or exactly or at
most 589, at least or exactly or at most 590, at least or exactly
or at most 591, at least or exactly or at most 592, at least or
exactly or at most 593, at least or exactly or at most 594, at
least or exactly or at most 595, at least or exactly or at most
596, at least or exactly or at most 597, at least or exactly or at
most 598, at least or exactly or at most 599, at least or exactly
or at most 600, at least or exactly or at most 601, at least or
exactly or at most 602, at least or exactly or at most 603, at
least or exactly or at most 604, at least or exactly or at most
605, at least or exactly or at most 606, at least or exactly or at
most 607, at least or exactly or at most 608, at least or exactly
or at most 609, at least or exactly or at most 610, at least or
exactly or at most 611, at least or exactly or at most 612, at
least or exactly or at most 613, at least or exactly or at most
614, at least or exactly or at most 615, at least or exactly or at
most 616, at least or exactly or at most 617, at least or exactly
or at most 618, at least or exactly or at most 619, at least or
exactly or at most 620, at least or exactly or at most 621, at
least or exactly or at most 622, at least or exactly or at most
623, at least or exactly or at most 624, at least or exactly or at
most 625, at least or exactly or at most 626, at least or exactly
or at most 627, at least or exactly or at most 628, at least or
exactly or at most 629, at least or exactly or at most 630, at
least or exactly or at most 631, at least or exactly or at most
632, at least or exactly or at most 633, at least or exactly or at
most 634, at least or exactly or at most 635, at least or exactly
or at most 636, at least or exactly or at most 637, at least or
exactly or at most 638, at least or exactly or at most 639, at
least or exactly or at most 640, at least or exactly or at most
641, at least or exactly or at most 642, at least or exactly or at
most 643, at least or exactly or at most 644, at least or exactly
or at most 645, at least or exactly or at most 646, at least or
exactly or at most 647, at least or exactly or at most 648, at
least or exactly or at most 649, at least or exactly or at most
650, at least or exactly or at most 651, at least or exactly or at
most 652, at least or exactly or at most 653, at least or exactly
or at most 654, at least or exactly or at most 655, at least or
exactly or at most 656, at least or exactly or at most 657, at
least or exactly or at most 658, at least or exactly or at most
659, at least or exactly or at most 660, at least or exactly or at
most 661, at least or exactly or at most 662, at least or exactly
or at most 663, at least or exactly or at most 664, at least or
exactly or at most 665, at least or exactly or at most 666, at
least or exactly or at most 667, at least or exactly or at most
668, at least or exactly or at most 669, at least or exactly or at
most 670, at least or exactly or at most 671, at least or exactly
or at most 672, at least or exactly or at most 673, at least or
exactly or at most 674, at least or exactly or at most 675, at
least or exactly or at most 676, at least or exactly or at most
677, at least or exactly or at most 678, at least or exactly or at
most 679, at least or exactly or at most 680, at least or exactly
or at most 681, at least or exactly or at most 682, at least or
exactly or at most 683, at least or exactly or at most 684, at
least or exactly or at most 685, at least or exactly or at most
686, at least or exactly or at most 687, at least or exactly or at
most 688, at least or exactly or at most 689, at least or exactly
or at most 690, at least or exactly or at most 691, at least or
exactly or at most 692, at least or exactly or at most 693, at
least or exactly or at most 694, at least or exactly or at most
695, at least or exactly or at most 696, at least or exactly or at
most 697, at least or exactly or at most 698, at least or exactly
or at most 699, at least or exactly or at most 700, at least or
exactly or at most 701, at least or exactly or at most 702, at
least or exactly or at most 703, at least or exactly or at most
704, at least or exactly or at most 705, at least or exactly or at
most 706, at least or exactly or at most 707, at least or exactly
or at most 708, at least or exactly or at most 709, at least or
exactly or at most 710, at least or exactly or at most 711
contiguous amino acid residues.
[0068] Insofar as embodiment b relates to SEQ ID NO: 21-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 712, at least or exactly
or at most 713, at least or exactly or at most 714, at least or
exactly or at most 715, at least or exactly or at most 716, at
least or exactly or at most 717, at least or exactly or at most
718, at least or exactly or at most 719, at least or exactly or at
most 720, at least or exactly or at most 721, at least or exactly
or at most 722, at least or exactly or at most 723, at least or
exactly or at most 724, at least or exactly or at most 725, at
least or exactly or at most 726, at least or exactly or at most 727
contiguous amino acid residues.
[0069] Insofar as embodiment b relates to SEQ ID NO: 22-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 728 contiguous amino acid
residues.
[0070] Insofar as embodiment b relates to SEQ ID NO: 23-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 729, at least or exactly
or at most 730, at least or exactly or at most 731, at least or
exactly or at most 732, at least or exactly or at most 733, at
least or exactly or at most 734, at least or exactly or at most
735, at least or exactly or at most 736, at least or exactly or at
most 737, at least or exactly or at most 738, at least or exactly
or at most 739, at least or exactly or at most 740, at least or
exactly or at most 741, at least or exactly or at most 742, at
least or exactly or at most 743, at least or exactly or at most
744, at least or exactly or at most 745, at least or exactly or at
most 746, at least or exactly or at most 747, at least or exactly
or at most 748, at least or exactly or at most 749, at least or
exactly or at most 750, at least or exactly or at most 751, at
least or exactly or at most 752, at least or exactly or at most
753, at least or exactly or at most 754 contiguous amino acid
residues.
[0071] Insofar as embodiment b relates to SEQ ID NO: 24-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 755, at least or exactly
or at most 756, at least or exactly or at most 757, at least or
exactly or at most 758, at least or exactly or at most 759, at
least or exactly or at most 760, at least or exactly or at most
761, at least or exactly or at most 762, at least or exactly or at
most 763, at least or exactly or at most 764, at least or exactly
or at most 765, at least or exactly or at most 766, at least or
exactly or at most 767, at least or exactly or at most 768, at
least or exactly or at most 769, at least or exactly or at most
770, at least or exactly or at most 771, at least or exactly or at
most 772, at least or exactly or at most 773, at least or exactly
or at most 774, at least or exactly or at most 775, at least or
exactly or at most 776, at least or exactly or at most 777, at
least or exactly or at most 778, at least or exactly or at most
779, at least or exactly or at most 780, at least or exactly or at
most 781, at least or exactly or at most 782, at least or exactly
or at most 783, at least or exactly or at most 784, at least or
exactly or at most 785, at least or exactly or at most 786, at
least or exactly or at most 787, at least or exactly or at most
788, at least or exactly or at most 789, at least or exactly or at
most 790, at least or exactly or at most 791, at least or exactly
or at most 792, at least or exactly or at most 793, at least or
exactly or at most 794, at least or exactly or at most 795, at
least or exactly or at most 796, at least or exactly or at most
797, at least or exactly or at most 798, at least or exactly or at
most 799, at least or exactly or at most 800, at least or exactly
or at most 801, at least or exactly or at most 802, at least or
exactly or at most 803, at least or exactly or at most 804, at
least or exactly or at most 805, at least or exactly or at most
806, at least or exactly or at most 807, at least or exactly or at
most 808, at least or exactly or at most 809, at least or exactly
or at most 810, at least or exactly or at most 811, at least or
exactly or at most 812, at least or exactly or at most 813, at
least or exactly or at most 814, at least or exactly or at most
815, at least or exactly or at most 816, at least or exactly or at
most 817, at least or exactly or at most 818, at least or exactly
or at most 819, at least or exactly or at most 820, at least or
exactly or at most 821, at least or exactly or at most 822, at
least or exactly or at most 823, at least or exactly or at most
824, at least or exactly or at most 825, at least or exactly or at
most 826, at least or exactly or at most 827, at least or exactly
or at most 828, at least or exactly or at most 829, at least or
exactly or at most 830, at least or exactly or at most 831, at
least or exactly or at most 832, at least or exactly or at most
833, at least or exactly or at most 834, at least or exactly or at
most 835, at least or exactly or at most 836, at least or exactly
or at most 837, at least or exactly or at most 838, at least or
exactly or at most 839, at least or exactly or at most 840, at
least or exactly or at most 841, at least or exactly or at most
842, at least or exactly or at most 843, at least or exactly or at
most 844, at least or exactly or at most 845, at least or exactly
or at most 846, at least or exactly or at most 847, at least or
exactly or at most 848, at least or exactly or at most 849, at
least or exactly or at most 850, at least or exactly or at most
851, at least or exactly or at most 852, at least or exactly or at
most 853, at least or exactly or at most 854, at least or exactly
or at most 855, at least or exactly or at most 856, at least or
exactly or at most 857, at least or exactly or at most 858, at
least or exactly or at most 859, at least or exactly or at most
860, at least or exactly or at most 861, at least or exactly or at
most 862, at least or exactly or at most 863, at least or exactly
or at most 864, at least or exactly or at most 865, at least or
exactly or at most 866, at least or exactly or at most 867, at
least or exactly or at most 868, at least or exactly or at most
869, at least or exactly or at most 870, at least or exactly or at
most 871, at least or exactly or at most 872, at least or exactly
or at most 873, at least or exactly or at most 874, at least or
exactly or at most 875, at least or exactly or at most 876, at
least or exactly or at most 877, at least or exactly or at most
878, at least or exactly or at most 879, at least or exactly or at
most 880, at least or exactly or at most 881, at least or exactly
or at most 882, at least or exactly or at most 883, at least or
exactly or at most 884, at least or exactly or at most 885, at
least or exactly or at most 886, at least or exactly or at most
887, at least or exactly or at most 888, at least or exactly or at
most 889, at least or exactly or at most 890, at least or exactly
or at most 891, at least or exactly or at most 892, at least or
exactly or at most 893, at least or exactly or at most 894, at
least or exactly or at most 895, at least or exactly or at most
896, at least or exactly or at most 897, at least or exactly or at
most 898, at least or exactly or at most 899, at least or exactly
or at most 900, at least or exactly or at most 901, at least or
exactly or at most 902, at least or exactly or at most 903, at
least or exactly or at most 904, at least or exactly or at most
905, at least or exactly or at most 906 contiguous amino acid
residues.
[0072] Insofar as embodiment b relates to SEQ ID NO: 25-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 907, at least or exactly
or at most 908, at least or exactly or at most 909, at least or
exactly or at most 910, at least or exactly or at most 911, at
least or exactly or at most 912, at least or exactly or at most
913, at least or exactly or at most 914, at least or exactly or at
most 915, at least or exactly or at most 916, at least or exactly
or at most 917, at least or exactly or at most 918, at least or
exactly or at most 919, at least or exactly or at most 920, at
least or exactly or at most 921, at least or exactly or at most
922, at least or exactly or at most 923, at least or exactly or at
most 924, at least or exactly or at most 925, at least or exactly
or at most 926, at least or exactly or at most 927, at least or
exactly or at most 928, at least or exactly or at most 929, at
least or exactly or at most 930, at least or exactly or at most
931, at least or exactly or at most 932, at least or exactly or at
most 933, at least or exactly or at most 934, at least or exactly
or at most 935, at least or exactly or at most 936, at least or
exactly or at most 937, at least or exactly or at most 938, at
least or exactly or at most 939, at least or exactly or at most
940, at least or exactly or at most 941, at least or exactly or at
most 942, at least or exactly or at most 943, at least or exactly
or at most 944, at least or exactly or at most 945, at least or
exactly or at most 946, at least or exactly or at most 947, at
least or exactly or at most 948, at least or exactly or at most
949, at least or exactly or at most 950, at least or exactly or at
most 951, at least or exactly or at most 952, at least or exactly
or at most 953, at least or exactly or at most 954, at least or
exactly or at most 955, at least or exactly or at most 956, at
least or exactly or at most 957, at least or exactly or at most
958, at least or exactly or at most 959, at least or exactly or at
most 960, at least or exactly or at most 961, at least or exactly
or at most 962, at least or exactly or at most 963, at least or
exactly or at most 964, at least or exactly or at most 965, at
least or exactly or at most 966, at least or exactly or at most
967, at least or exactly or at most 968, at least or exactly or at
most 969, at least or exactly or at most 970, at least or exactly
or at most 971, at least or exactly or at most 972, at least or
exactly or at most 973, at least or exactly or at most 974
contiguous amino acid residues.
[0073] Insofar as embodiment b relates to SEQ ID NO: 26-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 975, at least or exactly
or at most 976, at least or exactly or at most 977, at least or
exactly or at most 978, at least or exactly or at most 979, at
least or exactly or at most 980, at least or exactly or at most
981, at least or exactly or at most 982, at least or exactly or at
most 983, at least or exactly or at most 984, at least or exactly
or at most 985, at least or exactly or at most 986, at least or
exactly or at most 987, at least or exactly or at most 988, at
least or exactly or at most 989, at least or exactly or at most
990, at least or exactly or at most 991, at least or exactly or at
most 992, at least or exactly or at most 993, at least or exactly
or at most 994, at least or exactly or at most 995, at least or
exactly or at most 996, at least or exactly or at most 997, at
least or exactly or at most 998, at least or exactly or at most
999, at least or exactly or at most 1000, at least or exactly or at
most 1001, at least or exactly or at most 1002, at least or exactly
or at most 1003, at least or exactly or at most 1004, at least or
exactly or at most 1005, at least or exactly or at most 1006, at
least or exactly or at most 1007, at least or exactly or at most
1008, at least or exactly or at most 1009, at least or exactly or
at most 1010, at least or exactly or at most 1011, at least or
exactly or at most 1012, at least or exactly or at most 1013, at
least or exactly or at most 1014, at least or exactly or at most
1015, at least or exactly or at most 1016, at least or exactly or
at most 1017, at least or exactly or at most 1018, at least or
exactly or at most 1019, at least or exactly or at most 1020, at
least or exactly or at most 1021, at least or exactly or at most
1022, at least or exactly or at most 1023, at least or exactly or
at most 1024, at least or exactly or at most 1025, at least or
exactly or at most 1026, at least or exactly or at most 1027, at
least or exactly or at most 1028, at least or exactly or at most
1029, at least or exactly or at most 1030, at least or exactly or
at most 1031, at least or exactly or at most 1032, at least or
exactly or at most 1033, at least or exactly or at most 1034, at
least or exactly or at most 1035, at least or exactly or at most
1036, at least or exactly or at most 1037, at least or exactly or
at most 1038, at least or exactly or at most 1039, at least or
exactly or at most 1040, at least or exactly or at most 1041, at
least or exactly or at most 1042, at least or exactly or at most
1043, at least or exactly or at most 1044, at least or exactly or
at most 1045, at least or exactly or at most 1046, at least or
exactly or at most 1047, at least or exactly or at most 1048, at
least or exactly or at most 1049, at least or exactly or at most
1050, at least or exactly or at most 1051, at least or exactly or
at most 1052, at least or exactly or at most 1053, at least or
exactly or at most 1054, at least or exactly or at most 1055, at
least or exactly or at most 1056, at least or exactly or at most
1057, at least or exactly or at most 1058, at least or exactly or
at most 1059, at least or exactly or at most 1060, at least or
exactly or at most 1061, at least or exactly or at most 1062, at
least or exactly or at most 1063, at least or exactly or at most
1064, at least or exactly or at most 1065, at least or exactly or
at most 1066, at least or exactly or at most 1067, at least or
exactly or at most 1068, at least or exactly or at most 1069, at
least or exactly or at most 1070, at least or exactly or at most
1071 contiguous amino acid residues.
[0074] Insofar as embodiment b relates to SEQ ID NO: 27-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 1072, at least or exactly
or at most 1073, at least or exactly or at most 1074, at least or
exactly or at most 1075, at least or exactly or at most 1076, at
least or exactly or at most 1077, at least or exactly or at most
1078, at least or exactly or at most 1079, at least or exactly or
at most 1080, at least or exactly or at most 1081, at least or
exactly or at most 1082, at least or exactly or at most 1083, at
least or exactly or at most 1084, at least or exactly or at most
1085, at least or exactly or at most 1086, at least or exactly or
at most 1087, at least or exactly or at most 1088, at least or
exactly or at most 1089, at least or exactly or at most 1090, at
least or exactly or at most 1091, at least or exactly or at most
1092, at least or exactly or at most 1093, at least or exactly or
at most 1094, at least or exactly or at most 1095, at least or
exactly or at most 1096, at least or exactly or at most 1097, at
least or exactly or at most 1098, at least or exactly or at most
1099, at least or exactly or at most 1100, at least or exactly or
at most 1101, at least or exactly or at most 1102, at least or
exactly or at most 1103, at least or exactly or at most 1104, at
least or exactly or at most 1105, at least or exactly or at most
1106, at least or exactly or at most 1107, at least or exactly or
at most 1108, at least or exactly or at most 1109, at least or
exactly or at most 1110 contiguous amino acid residues.
[0075] Insofar as embodiment b relates to SEQ ID NO: 28-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 1111, at least or exactly
or at most 1112, at least or exactly or at most 1113, at least or
exactly or at most 1114, at least or exactly or at most 1115, at
least or exactly or at most 1116, at least or exactly or at most
1117, at least or exactly or at most 1118, at least or exactly or
at most 1119, at least or exactly or at most 1120, at least or
exactly or at most 1121, at least or exactly or at most 1122, at
least or exactly or at most 1123, at least or exactly or at most
1124, at least or exactly or at most 1125, at least or exactly or
at most 1126, at least or exactly or at most 1127, at least or
exactly or at most 1128, at least or exactly or at most 1129, at
least or exactly or at most 1130, at least or exactly or at most
1131, at least or exactly or at most 1132, at least or exactly or
at most 1133, at least or exactly or at most 1134, at least or
exactly or at most 1135, at least or exactly or at most 1136, at
least or exactly or at most 1137, at least or exactly or at most
1138, at least or exactly or at most 1139, at least or exactly or
at most 1140, at least or exactly or at most 1141, at least or
exactly or at most 1142, at least or exactly or at most 1143, at
least or exactly or at most 1144, at least or exactly or at most
1145, at least or exactly or at most 1146, at least or exactly or
at most 1147, at least or exactly or at most 1148, at least or
exactly or at most 1149, at least or exactly or at most 1150, at
least or exactly or at most 1151, at least or exactly or at most
1152, at least or exactly or at most 1153, at least or exactly or
at most 1154, at least or exactly or at most 1155, at least or
exactly or at most 1156, at least or exactly or at most 1157, at
least or exactly or at most 1158, at least or exactly or at most
1159, at least or exactly or at most 1160, at least or exactly or
at most 1161, at least or exactly or at most 1162, at least or
exactly or at most 1163, at least or exactly or at most 1164, at
least or exactly or at most 1165, at least or exactly or at most
1166, at least or exactly or at most 1167, at least or exactly or
at most 1168, at least or exactly or at most 1169, at least or
exactly or at most 1170, at least or exactly or at most 1171, at
least or exactly or at most 1172, at least or exactly or at most
1173, at least or exactly or at most 1174, at least or exactly or
at most 1175, at least or exactly or at most 1176, at least or
exactly or at most 1177, at least or exactly or at most 1178, at
least or exactly or at most 1179, at least or exactly or at most
1180, at least or exactly or at most 1181, at least or exactly or
at most 1182, at least or exactly or at most 1183, at least or
exactly or at most 1184, at least or exactly or at most 1185, at
least or exactly or at most 1186, at least or exactly or at most
1187, at least or exactly or at most 1188, at least or exactly or
at most 1189, at least or exactly or at most 1190, at least or
exactly or at most 1191, at least or exactly or at most 1192, at
least or exactly or at most 1193, at least or exactly or at most
1194, at least or exactly or at most 1195, at least or exactly or
at most 1196, at least or exactly or at most 1197, at least or
exactly or at most 1198, at least or exactly or at most 1199, at
least or exactly or at most 1200, at least or exactly or at most
1201, at least or exactly or at most 1202, at least or exactly or
at most 1203, at least or exactly or at most 1204, at least or
exactly or at most 1205, at least or exactly or at most 1206, at
least or exactly or at most 1207, at least or exactly or at most
1208, at least or exactly or at most 1209, at least or exactly or
at most 1210, at least or exactly or at most 1211, at least or
exactly or at most 1212, at least or exactly or at most 1213, at
least or exactly or at most 1214, at least or exactly or at most
1215, at least or exactly or at most 1216, at least or exactly or
at most 1217, at least or exactly or at most 1218, at least or
exactly or at most 1219, at least or exactly or at most 1220, at
least or exactly or at most 1221, at least or exactly or at most
1222, at least or exactly or at most 1223, at least or exactly or
at most 1224, at least or exactly or at most 1225, at least or
exactly or at most 1226, at least or exactly or at most 1227, at
least or exactly or at most 1228 contiguous amino acid
residues.
[0076] Insofar as embodiment b relates to SEQ ID NO: 29-30, the at
least 5 contiguous amino acids referred to in option b) in the
definition of the first aspect of the invention will preferably
constitute at least or exactly or at most 1229, at least or exactly
or at most 1230, at least or exactly or at most 1231, at least or
exactly or at most 1232, at least or exactly or at most 1233, at
least or exactly or at most 1234, at least or exactly or at most
1235, at least or exactly or at most 1236, at least or exactly or
at most 1237, at least or exactly or at most 1238, at least or
exactly or at most 1239, at least or exactly or at most 1240, at
least or exactly or at most 1241, at least or exactly or at most
1242, at least or exactly or at most 1243, at least or exactly or
at most 1244, at least or exactly or at most 1245, at least or
exactly or at most 1246, at least or exactly or at most 1247, at
least or exactly or at most 1248, at least or exactly or at most
1249, at least or exactly or at most 1250, at least or exactly or
at most 1251, at least or exactly or at most 1252, at least or
exactly or at most 1253, at least or exactly or at most 1254, at
least or exactly or at most 1255, at least or exactly or at most
1256, at least or exactly or at most 1257, at least or exactly or
at most 1258, at least or exactly or at most 1259, at least or
exactly or at most 1260, at least or exactly or at most 1261, at
least or exactly or at most 1262, at least or exactly or at most
1263, at least or exactly or at most 1264, at least or exactly or
at most 1265, at least or exactly or at most 1266, at least or
exactly or at most 1267, at least or exactly or at most 1268, at
least or exactly or at most 1269, at least or exactly or at most
1270, at least or exactly or at most 1271, at least or exactly or
at most 1272, at least or exactly or at most 1273, at least or
exactly or at most 1274, at least or exactly or at most 1275, at
least or exactly or at most 1276, at least or exactly or at most
1277, at least or exactly or at most 1278, at least or exactly or
at most 1279, at least or exactly or at most 1280, at least or
exactly or at most 1281, at least or exactly or at most 1282, at
least or exactly or at most 1283, at least or exactly or at most
1284 contiguous amino acid residues.
Insofar as embodiment b relates to SEQ ID NO: 30, the at least 5
contiguous amino acids referred to in option b) in the definition
of the first aspect of the invention will preferably constitute at
least or exactly or at most 1285, at least or exactly or at most
1286, at least or exactly or at most 1287, at least or exactly or
at most 1288, at least or exactly or at most 1289, at least or
exactly or at most 1290, at least or exactly or at most 1291, at
least or exactly or at most 1292, at least or exactly or at most
1293, at least or exactly or at most 1294, at least or exactly or
at most 1295, at least or exactly or at most 1296, at least or
exactly or at most 1297, at least or exactly or at most 1298, at
least or exactly or at most 1299, at least or exactly or at most
1300, at least or exactly or at most 1301, at least or exactly or
at most 1302, at least or exactly or at most 1303, at least or
exactly or at most 1304, at least or exactly or at most 1305, at
least or exactly or at most 1306, at least or exactly or at most
1307, at least or exactly or at most 1308, at least or exactly or
at most 1309, at least or exactly or at most 1310, at least or
exactly or at most 1311, at least or exactly or at most 1312, at
least or exactly or at most 1313, at least or exactly or at most
1314, at least or exactly or at most 1315, at least or exactly or
at most 1316, at least or exactly or at most 1317, at least or
exactly or at most 1318, at least or exactly or at most 1319, at
least or exactly or at most 1320, at least or exactly or at most
1321, at least or exactly or at most 1322, at least or exactly or
at most 1323, at least or exactly or at most 1324, at least or
exactly or at most 1325, at least or exactly or at most 1326, at
least or exactly or at most 1327, at least or exactly or at most
1328, at least or exactly or at most 1329, at least or exactly or
at most 1330, at least or exactly or at most 1331, at least or
exactly or at most 1332, at least or exactly or at most 1333, at
least or exactly or at most 1334, at least or exactly or at most
1335, at least or exactly or at most 1336, at least or exactly or
at most 1337, at least or exactly or at most 1338, at least or
exactly or at most 1339, at least or exactly or at most 1340, at
least or exactly or at most 1341, at least or exactly or at most
1342, at least or exactly or at most 1343, at least or exactly or
at most 1344, at least or exactly or at most 1345, at least or
exactly or at most 1346, at least or exactly or at most 1347, at
least or exactly or at most 1348, at least or exactly or at most
1349, at least or exactly or at most 1350, at least or exactly or
at most 1351, at least or exactly or at most 1352, at least or
exactly or at most 1353, at least or exactly or at most 1354, at
least or exactly or at most 1355, at least or exactly or at most
1356, at least or exactly or at most 1357, at least or exactly or
at most 1358, at least or exactly or at most 1359, at least or
exactly or at most 1360, at least or exactly or at most 1361, at
least or exactly or at most 1362, at least or exactly or at most
1363, at least or exactly or at most 1364, at least or exactly or
at most 1365, at least or exactly or at most 1366, at least or
exactly or at most 1367, at least or exactly or at most 1368, at
least or exactly or at most 1369, at least or exactly or at most
1370, at least or exactly or at most 1371, at least or exactly or
at most 1372, at least or exactly or at most 1373, at least or
exactly or at most 1374, at least or exactly or at most 1375, at
least or exactly or at most 1376, at least or exactly or at most
1377, at least or exactly or at most 1378, at least or exactly or
at most 1379, at least or exactly or at most 1380, at least or
exactly or at most 1381, at least or exactly or at most 1382, at
least or exactly or at most 1383, at least or exactly or at most
1384, at least or exactly or at most 1385, at least or exactly or
at most 1386, at least or exactly or at most 1387, at least or
exactly or at most 1388, at least or exactly or at most 1389, at
least or exactly or at most 1390, at least or exactly or at most
1391, at least or exactly or at most 1392, at least or exactly or
at most 1393, at least or exactly or at most 1394, at least or
exactly or at most 1395, at least or exactly or at most 1396, at
least or exactly or at most 1397, at least or exactly or at most
1398, at least or exactly or at most 1399, at least or exactly or
at most 1400, at least or exactly or at most 1401, at least or
exactly or at most 1402, at least or exactly or at most 1403, at
least or exactly or at most 1404, at least or exactly or at most
1405, at least or exactly or at most 1406, at least or exactly or
at most 1407, at least or exactly or at most 1408, at least or
exactly or at most 1409, at least or exactly or at most 1410, at
least or exactly or at most 1411, at least or exactly or at most
1412, at least or exactly or at most 1413, at least or exactly or
at most 1414, at least or exactly or at most 1415, at least or
exactly or at most 1416, at least or exactly or at most 1417, at
least or exactly or at most 1418, at least or exactly or at most
1419, at least or exactly or at most 1420, at least or exactly or
at most 1421, at least or exactly or at most 1422, at least or
exactly or at most 1423, at least or exactly or at most 1424, at
least or exactly or at most 1425, at least or exactly or at most
1426, at least or exactly or at most 1427, at least or exactly or
at most 1428, at least or exactly or at most 1429, at least or
exactly or at most 1430, at least or exactly or at most 1431, at
least or exactly or at most 1432, at least or exactly or at most
1433, at least or exactly or at most 1434, at least or exactly or
at most 1435, at least or exactly or at most 1436, at least or
exactly or at most 1437, at least or exactly or at most 1438, at
least or exactly or at most 1439, at least or exactly or at most
1440, at least or exactly or at most 1441, at least or exactly or
at most 1442, at least or exactly or at most 1443, at least or
exactly or at most 1444, at least or exactly or at most 1445, at
least or exactly or at most 1446, at least or exactly or at most
1447, at least or exactly or at most 1448, at least or exactly or
at most 1449, at least or exactly or at most 1450, at least or
exactly or at most 1451, at least or exactly or at most 1452, at
least or exactly or at most 1453, at least or exactly or at most
1454, at least or exactly or at most 1455, at least or exactly or
at most 1456, at least or exactly or at most 1457, at least or
exactly or at most 1458, at least or exactly or at most 1459, at
least or exactly or at most 1460, at least or exactly or at most
1461, at least or exactly or at most 1462, at least or exactly or
at most 1463, at least or exactly or at most 1464, at least or
exactly or at most 1465, at least or exactly or at most 1466, at
least or exactly or at most 1467, at least or exactly or at most
1468, at least or exactly or at most 1469, at least or exactly or
at most 1470, at least or exactly or at most 1471, at least or
exactly or at most 1472, at least or exactly or at most 1473, at
least or exactly or at most 1474, at least or exactly or at most
1475, at least or exactly or at most 1476, at least or exactly or
at most 1477, at least or exactly or at most 1478, at least or
exactly or at most 1479, at least or exactly or at most 1480, at
least or exactly or at most 1481, at least or exactly or at most
1482, at least or exactly or at most 1483, at least or exactly or
at most 1484, at least or exactly or at most 1485, at least or
exactly or at most 1486, at least or exactly or at most 1487, at
least or exactly or at most 1488, at least or exactly or at most
1489, at least or exactly or at most 1490, at least or exactly or
at most 1491, at least or exactly or at most 1492, at least or
exactly or at most 1493, at least or exactly or at most 1494, at
least or exactly or at most 1495, at least or exactly or at most
1496, at least or exactly or at most 1497, at least or exactly or
at most 1498, at least or exactly or at most 1499, at least or
exactly or at most 1500, at least or exactly or at most 1501, at
least or exactly or at most 1502, at least or exactly or at most
1503, at least or exactly or at most 1504, at least or exactly or
at most 1505, at least or exactly or at most 1506, at least or
exactly or at most 1507, at least or exactly or at most 1508, at
least or exactly or at most 1509, at least or exactly or at most
1510, at least or exactly or at most 1511, at least or exactly or
at most 1512, at least or exactly or at most 1513, at least or
exactly or at most 1514, at least or exactly or at most 1515, at
least or exactly or at most 1516, at least or exactly or at most
1517, at least or exactly or at most 1518, at least or exactly or
at most 1519, at least or exactly or at most 1520, at least or
exactly or at most 1521, at least or exactly or at most 1522, at
least or exactly or at most 1523, at least or exactly or at most
1524, at least or exactly or at most 1525, at least or exactly or
at most 1526, at least or exactly or at most 1527, at least or
exactly or at most 1528, at least or exactly or at most 1529, at
least or exactly or at most 1530, at least or exactly or at most
1531, at least or exactly or at most 1532, at least or exactly or
at most 1533, at least or exactly or at most 1534, at least or
exactly or at most 1535, at least or exactly or at most 1536, at
least or exactly or at most 1537, at least or exactly or at most
1538, at least or exactly or at most 1539, at least or exactly or
at most 1540, at least or exactly or at most 1541, at least or
exactly or at most 1542, at least or exactly or at most 1543, at
least or exactly or at most 1544, at least or exactly or at most
1545, at least or exactly or at most 1546, at least or exactly or
at most 1547, at least or exactly or at most 1548, at least or
exactly or at most 1549, at least or exactly or at most 1550, at
least or exactly or at most 1551, at least or exactly or at most
1552, at least or exactly or at most 1553, at least or exactly or
at most 1554, at least or exactly or at most 1555, at least or
exactly or at most 1556, at least or exactly or at most 1557, at
least or exactly or at most 1558, at least or exactly or at most
1559, at least or exactly or at most 1560, at least or exactly or
at most 1561, at least or exactly or at most 1562, at least or
exactly or at most 1563, at least or exactly or at most 1564, at
least or exactly or at most 1565, at least or exactly or at most
1566, at least or exactly or at most 1567, at least or exactly or
at most 1568, at least or exactly or at most 1569, at least or
exactly or at most 1570, at least or exactly or at most 1571, at
least or exactly or at most 1572, at least or exactly or at most
1573, at least or exactly or at most 1574, at least or exactly or
at most 1575, at least or exactly or at most 1576, at least or
exactly or at most 1577, at least or exactly or at most 1578, at
least or exactly or at most 1579, at least or exactly or at most
1580, at least or exactly or at most 1581, at least or exactly or
at most 1582, at least or exactly or at most 1583, at least or
exactly or at most 1584, at least or exactly or at most 1585, at
least or exactly or at most 1586, at least or exactly or at most
1587, at least or exactly or at most 1588, at least or exactly or
at most 1589, at least or exactly or at most 1590, at least or
exactly or at most 1591, at least or exactly or at most 1592, at
least or exactly or at most 1593, at least or exactly or at most
1594, at least or exactly or at most 1595, at least or exactly or
at most 1596, at least or exactly or at most 1597, at least or
exactly or at most 1598, at least or exactly or at most 1599, at
least or exactly or at most 1600, at least or exactly or at most
1601, at least or exactly or at most 1602, at least or exactly or
at most 1603, at least or exactly or at most 1604, at least or
exactly or at most 1605, at least or exactly or at most 1606, at
least or exactly or at most 1607, at least or exactly or at most
1608, at least or exactly or at most 1609, at least or exactly or
at most 1610, at least or exactly or at most 1611, at least or
exactly or at most 1612, at least or exactly or at most 1613, at
least or exactly or at most 1614, at least or exactly or at most
1615, at least or exactly or at most 1616, at least or exactly or
at most 1617, at least or exactly or at most 1618, at least or
exactly or at most 1619, at least or exactly or at most 1620, at
least or exactly or at most 1621, at least or exactly or at most
1622, at least or exactly or at most 1623, at least or exactly or
at most 1624, at least or exactly or at most 1625, at least or
exactly or at most 1626, at least or exactly or at most 1627, at
least or exactly or at most 1628, at least or exactly or at most
1629, at least or exactly or at most 1630, at least or exactly or
at most 1631, at least or exactly or at most 1632, at least or
exactly or at most 1633, at least or exactly or at most 1634, at
least or exactly or at most 1635, at least or exactly or at most
1636, at least or exactly or at most 1637, at least or exactly or
at most 1638, at least or exactly or at most 1639, at least or
exactly or at most 1640, at least or exactly or at most 1641, at
least or exactly or at most 1642, at least or exactly or at most
1643, at least or exactly or at most 1644, at least or exactly or
at most 1645, at least or exactly or at most 1646, at least or
exactly or at most 1647, at least or exactly or at most 1648, at
least or exactly or at most 1649, at least or exactly or at most
1650, at least or exactly or at most 1651, at least or exactly or
at most 1652, at least or exactly or at most 1653, at least or
exactly or at most 1654, at least or exactly or at most 1655, at
least or exactly or at most 1656, at least or exactly or at most
1657, at least or exactly or at most 1658, at least or exactly or
at most 1659, at least or exactly or at most 1660, at least or
exactly or at most 1661, at least or exactly or at most 1662, at
least or exactly or at most 1663, at least or exactly or at most
1664, at least or exactly or at most 1665, at least or exactly or
at most 1666, at least or exactly or at most 1667, at least or
exactly or at most 1668, at least or exactly or at most 1669, at
least or exactly or at most 1670, at least or exactly or at most
1671, at least or exactly or at most 1672, at least or exactly or
at most 1673, at least or exactly or at most 1674, at least or
exactly or at most 1675, at least or exactly or at most 1676, at
least or exactly or at most 1677, at least or exactly or at most
1678, at least or exactly or at most 1679, at least or exactly or
at most 1680, at least or exactly or at most 1681, at least or
exactly or at most 1682, at least or exactly or at most 1683, at
least or exactly or at most 1684, at least or exactly or at most
1685, at least or exactly or at most 1686, at least or exactly or
at most 1687, at least or exactly or at most 1688, at least or
exactly or at most 1689, at least or exactly or at most 1690, at
least or exactly or at most 1691, at least or exactly or at most
1692, at least or exactly or at most 1693, at least or exactly or
at most 1694, at least or exactly or at most 1695, at least or
exactly or at most 1696, at least or exactly or at most 1697, at
least or exactly or at most 1698, at least or exactly or at most
1699, at least or exactly or at most 1700, at least or exactly or
at most 1701, at least or exactly or at most 1702, at least or
exactly or at most 1703, at least or exactly or at most 1704, at
least or exactly or at most 1705, at least or exactly or at most
1706, at least or exactly or at most 1707, at least or exactly or
at most 1708, at least or exactly or at most 1709, at least or
exactly or at most 1710, at least or exactly or at most 1711, at
least or exactly or at most 1712, at least or exactly or at most
1713, at least or exactly or at most 1714, at least or exactly or
at most 1715, at least or exactly or at most 1716, at least or
exactly or at most 1717, at least or exactly or at most 1718, at
least or exactly or at most 1719, at least or exactly or at most
1720, at least or exactly or at most 1721, at least or exactly or
at most 1722, at least or exactly or at most 1723, at least or
exactly or at most 1724, at least or exactly or at most 1725, at
least or exactly or at most 1726, at least or exactly or at most
1727, at least or exactly or at most 1728, at least or exactly or
at most 1729, at least or exactly or at most 1730, at least or
exactly or at most 1731, at least or exactly or at most 1732, at
least or exactly or at most 1733, at least or exactly or at most
1734, at least or exactly or at most 1735, at least or exactly or
at most 1736, at least or exactly or at most 1737, at least or
exactly or at most 1738, at least or exactly or at most 1739, at
least or exactly or at most 1740, at least or exactly or at most
1741, at least or exactly or at most 1742, at least or exactly or
at most 1743, at least or exactly or at most 1744, at least or
exactly or at most 1745, at least or exactly or at most 1746, at
least or exactly or at most 1747, at least or exactly or at most
1748, at least or exactly or at most 1749, at least or exactly or
at most 1750, at least or exactly or at most 1751, at least or
exactly or at most 1752, at least or exactly or at most 1753, at
least or exactly or at most 1754, at least or exactly or at most
1755, at least or exactly or at most 1756, at least or exactly or
at most 1757, at least or exactly or at most 1758, at least or
exactly or at most 1759, at least or exactly or at most 1760, at
least or exactly or at most 1761, at least or exactly or at most
1762, at least or exactly or at most 1763, at least or exactly or
at most 1764, at least or exactly or at most 1765, at least or
exactly or at most 1766, at least or exactly or at most 1767, at
least or exactly or at most 1768, at least or exactly or at most
1769, at least or exactly or at most 1770, at least or exactly or
at most 1771, at least or exactly or at most 1772, at least or
exactly or at most 1773, at least or exactly or at most 1774, at
least or exactly or at most 1775, at least or exactly or at most
1776, at least or exactly or at most 1777, at least or exactly or
at most 1778, at least or exactly or at most 1779, at least or
exactly or at most 1780, at least or
exactly or at most 1781, at least or exactly or at most 1782, at
least or exactly or at most 1783, at least or exactly or at most
1784, at least or exactly or at most 1785, at least or exactly or
at most 1786, at least or exactly or at most 1787, at least or
exactly or at most 1788, at least or exactly or at most 1789, at
least or exactly or at most 1790, at least or exactly or at most
1791, at least or exactly or at most 1792, at least or exactly or
at most 1793, at least or exactly or at most 1794, at least or
exactly or at most 1795, at least or exactly or at most 1796, at
least or exactly or at most 1797, at least or exactly or at most
1798, at least or exactly or at most 1799, at least or exactly or
at most 1800, at least or exactly or at most 1801, at least or
exactly or at most 1802, at least or exactly or at most 1803, at
least or exactly or at most 1804, at least or exactly or at most
1805, at least or exactly or at most 1806, at least or exactly or
at most 1807, at least or exactly or at most 1808, at least or
exactly or at most 1809, at least or exactly or at most 1810, at
least or exactly or at most 1811, at least or exactly or at most
1812, at least or exactly or at most 1813, at least or exactly or
at most 1814, at least or exactly or at most 1815, at least or
exactly or at most 1816, at least or exactly or at most 1817, at
least or exactly or at most 1818, at least or exactly or at most
1819, at least or exactly or at most 1820, at least or exactly or
at most 1821, at least or exactly or at most 1822, at least or
exactly or at most 1823, at least or exactly or at most 1824, at
least or exactly or at most 1825, at least or exactly or at most
1826, at least or exactly or at most 1827, at least or exactly or
at most 1828, at least or exactly or at most 1829, at least or
exactly or at most 1830, at least or exactly or at most 1831, at
least or exactly or at most 1832, at least or exactly or at most
1833, at least or exactly or at most 1834, at least or exactly or
at most 1835, at least or exactly or at most 1836, at least or
exactly or at most 1837, at least or exactly or at most 1838, at
least or exactly or at most 1839, at least or exactly or at most
1840, at least or exactly or at most 1841, at least or exactly or
at most 1842, at least or exactly or at most 1843, at least or
exactly or at most 1844, at least or exactly or at most 1845, at
least or exactly or at most 1846, at least or exactly or at most
1847, at least or exactly or at most 1848, at least or exactly or
at most 1849, at least or exactly or at most 1850, at least or
exactly or at most 1851, at least or exactly or at most 1852, at
least or exactly or at most 1853, at least or exactly or at most
1854, at least or exactly or at most 1855, at least or exactly or
at most 1856, at least or exactly or at most 1857, at least or
exactly or at most 1858, at least or exactly or at most 1859, at
least or exactly or at most 1860, at least or exactly or at most
1861, at least or exactly or at most 1862, at least or exactly or
at most 1863, at least or exactly or at most 1864, at least or
exactly or at most 1865, at least or exactly or at most 1866, at
least or exactly or at most 1867, at least or exactly or at most
1868, at least or exactly or at most 1869, at least or exactly or
at most 1870, at least or exactly or at most 1871, at least or
exactly or at most 1872, at least or exactly or at most 1873, at
least or exactly or at most 1874, at least or exactly or at most
1875, at least or exactly or at most 1876, at least or exactly or
at most 1877, at least or exactly or at most 1878, at least or
exactly or at most 1879, at least or exactly or at most 1880, at
least or exactly or at most 1881, at least or exactly or at most
1882, at least or exactly or at most 1883, at least or exactly or
at most 1884, at least or exactly or at most 1885, at least or
exactly or at most 1886, at least or exactly or at most 1887, at
least or exactly or at most 1888, at least or exactly or at most
1889, at least or exactly or at most 1890, at least or exactly or
at most 1891, at least or exactly or at most 1892, at least or
exactly or at most 1893, at least or exactly or at most 1894, at
least or exactly or at most 1895, at least or exactly or at most
1896, at least or exactly or at most 1897, at least or exactly or
at most 1898, at least or exactly or at most 1899, at least or
exactly or at most 1900, at least or exactly or at most 1901, at
least or exactly or at most 1902, at least or exactly or at most
1903, at least or exactly or at most 1904, at least or exactly or
at most 1905, at least or exactly or at most 1906, at least or
exactly or at most 1907, at least or exactly or at most 1908, at
least or exactly or at most 1909, at least or exactly or at most
1910, at least or exactly or at most 1911, at least or exactly or
at most 1912, at least or exactly or at most 1913, at least or
exactly or at most 1914, at least or exactly or at most 1915, at
least or exactly or at most 1916, at least or exactly or at most
1917, at least or exactly or at most 1918, at least or exactly or
at most 1919, at least or exactly or at most 1920, at least or
exactly or at most 1921, at least or exactly or at most 1922, at
least or exactly or at most 1923, at least or exactly or at most
1924, at least or exactly or at most 1925, at least or exactly or
at most 1926, at least or exactly or at most 1927, at least or
exactly or at most 1928, at least or exactly or at most 1929, at
least or exactly or at most 1930, at least or exactly or at most
1931, at least or exactly or at most 1932, at least or exactly or
at most 1933, at least or exactly or at most 1934, at least or
exactly or at most 1935, at least or exactly or at most 1936, at
least or exactly or at most 1937, at least or exactly or at most
1938, at least or exactly or at most 1939, at least or exactly or
at most 1940, at least or exactly or at most 1941, at least or
exactly or at most 1942, at least or exactly or at most 1943, at
least or exactly or at most 1944, at least or exactly or at most
1945, at least or exactly or at most 1946, at least or exactly or
at most 1947, at least or exactly or at most 1948, at least or
exactly or at most 1949, at least or exactly or at most 1950, at
least or exactly or at most 1951, at least or exactly or at most
1952, at least or exactly or at most 1953, at least or exactly or
at most 1954, at least or exactly or at most 1955, at least or
exactly or at most 1956, at least or exactly or at most 1957, at
least or exactly or at most 1958, at least or exactly or at most
1959, at least or exactly or at most 1960, at least or exactly or
at most 1961, at least or exactly or at most 1962, at least or
exactly or at most 1963, at least or exactly or at most 1964, at
least or exactly or at most 1965, at least or exactly or at most
1966, at least or exactly or at most 1967, at least or exactly or
at most 1968, at least or exactly or at most 1969, at least or
exactly or at most 1970, at least or exactly or at most 1971, at
least or exactly or at most 1972, at least or exactly or at most
1973, at least or exactly or at most 1974, at least or exactly or
at most 1975, at least or exactly or at most 1976, at least or
exactly or at most 1977, at least or exactly or at most 1978, at
least or exactly or at most 1979, at least or exactly or at most
1980, at least or exactly or at most 1981, at least or exactly or
at most 1982, at least or exactly or at most 1983, at least or
exactly or at most 1984, at least or exactly or at most 1985, at
least or exactly or at most 1986, at least or exactly or at most
1987, at least or exactly or at most 1988, at least or exactly or
at most 1989, at least or exactly or at most 1990, at least or
exactly or at most 1991, at least or exactly or at most 1992, at
least or exactly or at most 1993, at least or exactly or at most
1994, at least or exactly or at most 1995, at least or exactly or
at most 1996, at least or exactly or at most 1997, at least or
exactly or at most 1998, at least or exactly or at most 1999, at
least or exactly or at most 2000, at least or exactly or at most
2001, at least or exactly or at most 2002, at least or exactly or
at most 2003, at least or exactly or at most 2004, at least or
exactly or at most 2005, at least or exactly or at most 2006, at
least or exactly or at most 2007, at least or exactly or at most
2008, at least or exactly or at most 2009, at least or exactly or
at most 2010, at least or exactly or at most 2011, at least or
exactly or at most 2012, at least or exactly or at most 2013, at
least or exactly or at most 2014, at least or exactly or at most
2015, at least or exactly or at most 2016, at least or exactly or
at most 2017, at least or exactly or at most 2018, at least or
exactly or at most 2019, at least or exactly or at most 2020, at
least or exactly or at most 2021, at least or exactly or at most
2022, at least or exactly or at most 2023, at least or exactly or
at most 2024, at least or exactly or at most 2025, at least or
exactly or at most 2026, at least or exactly or at most 2027, at
least or exactly or at most 2028, at least or exactly or at most
2029, at least or exactly or at most 2030, at least or exactly or
at most 2031, at least or exactly or at most 2032, at least or
exactly or at most 2033, at least or exactly or at most 2034, at
least or exactly or at most 2035, at least or exactly or at most
2036, at least or exactly or at most 2037, at least or exactly or
at most 2038, at least or exactly or at most 2039, at least or
exactly or at most 2040, at least or exactly or at most 2041, at
least or exactly or at most 2042, at least or exactly or at most
2043, at least or exactly or at most 2044, at least or exactly or
at most 2045, at least or exactly or at most 2046, at least or
exactly or at most 2047, at least or exactly or at most 2048, at
least or exactly or at most 2049, at least or exactly or at most
2050, at least or exactly or at most 2051, at least or exactly or
at most 2052, at least or exactly or at most 2053, at least or
exactly or at most 2054, at least or exactly or at most 2055, at
least or exactly or at most 2056, at least or exactly or at most
2057, at least or exactly or at most 2058, at least or exactly or
at most 2059, at least or exactly or at most 2060, at least or
exactly or at most 2061, at least or exactly or at most 2062, at
least or exactly or at most 2063, at least or exactly or at most
2064, at least or exactly or at most 2065, at least or exactly or
at most 2066, at least or exactly or at most 2067, at least or
exactly or at most 2068, at least or exactly or at most 2069, at
least or exactly or at most 2070, at least or exactly or at most
2071, at least or exactly or at most 2072, at least or exactly or
at most 2073, at least or exactly or at most 2074, at least or
exactly or at most 2075, at least or exactly or at most 2076, at
least or exactly or at most 2077, at least or exactly or at most
2078, at least or exactly or at most 2079, at least or exactly or
at most 2080, at least or exactly or at most 2081, at least or
exactly or at most 2082, at least or exactly or at most 2083, at
least or exactly or at most 2084, at least or exactly or at most
2085, at least or exactly or at most 2086, at least or exactly or
at most 2087, at least or exactly or at most 2088, at least or
exactly or at most 2089, at least or exactly or at most 2090, at
least or exactly or at most 2091, at least or exactly or at most
2092, at least or exactly or at most 2093, at least or exactly or
at most 2094, at least or exactly or at most 2095, at least or
exactly or at most 2096, at least or exactly or at most 2097, at
least or exactly or at most 2098, at least or exactly or at most
2099, at least or exactly or at most 2100, at least or exactly or
at most 2101, at least or exactly or at most 2102, at least or
exactly or at most 2103, at least or exactly or at most 2104, at
least or exactly or at most 2105, at least or exactly or at most
2106, at least or exactly or at most 2107, at least or exactly or
at most 2108, at least or exactly or at most 2109, at least or
exactly or at most 2110, at least or exactly or at most 2111, at
least or exactly or at most 2112, at least or exactly or at most
2113, at least or exactly or at most 2114, at least or exactly or
at most 2115, at least or exactly or at most 2116, at least or
exactly or at most 2117, at least or exactly or at most 2118, at
least or exactly or at most 2119, at least or exactly or at most
2120, at least or exactly or at most 2121, at least or exactly or
at most 2122, at least or exactly or at most 2123, at least or
exactly or at most 2124, at least or exactly or at most 2125, at
least or exactly or at most 2126, at least or exactly or at most
2127, at least or exactly or at most 2128, at least or exactly or
at most 2129, at least or exactly or at most 2130, at least or
exactly or at most 2131, at least or exactly or at most 2132, at
least or exactly or at most 2133, at least or exactly or at most
2134, at least or exactly or at most 2135, at least or exactly or
at most 2136, at least or exactly or at most 2137, at least or
exactly or at most 2138, at least or exactly or at most 2139, at
least or exactly or at most 2140, at least or exactly or at most
2141, at least or exactly or at most 2142, at least or exactly or
at most 2143, at least or exactly or at most 2144, at least or
exactly or at most 2145, at least or exactly or at most 2146, at
least or exactly or at most 2147, at least or exactly or at most
2148, at least or exactly or at most 2149, at least or exactly or
at most 2150, at least or exactly or at most 2151, at least or
exactly or at most 2152, at least or exactly or at most 2153, at
least or exactly or at most 2154, at least or exactly or at most
2155, at least or exactly or at most 2156, at least or exactly or
at most 2157, at least or exactly or at most 2158, at least or
exactly or at most 2159, at least or exactly or at most 2160, at
least or exactly or at most 2161, at least or exactly or at most
2162, at least or exactly or at most 2163, at least or exactly or
at most 2164, at least or exactly or at most 2165, at least or
exactly or at most 2166, at least or exactly or at most 2167, at
least or exactly or at most 2168, at least or exactly or at most
2169, at least or exactly or at most 2170, at least or exactly or
at most 2171, at least or exactly or at most 2172, at least or
exactly or at most 2173, at least or exactly or at most 2174, at
least or exactly or at most 2175, at least or exactly or at most
2176, at least or exactly or at most 2177, at least or exactly or
at most 2178, at least or exactly or at most 2179, at least or
exactly or at most 2180, at least or exactly or at most 2181, at
least or exactly or at most 2182, at least or exactly or at most
2183, at least or exactly or at most 2184, at least or exactly or
at most 2185, at least or exactly or at most 2186, at least or
exactly or at most 2187, at least or exactly or at most 2188, at
least or exactly or at most 2189, at least or exactly or at most
2190, at least or exactly or at most 2191, at least or exactly or
at most 2192, at least or exactly or at most 2193, at least or
exactly or at most 2194, at least or exactly or at most 2195, at
least or exactly or at most 2196, at least or exactly or at most
2197, at least or exactly or at most 2198, at least or exactly or
at most 2199, at least or exactly or at most 2200, at least or
exactly or at most 2201, at least or exactly or at most 2202, at
least or exactly or at most 2203, at least or exactly or at most
2204, at least or exactly or at most 2205, at least or exactly or
at most 2206, at least or exactly or at most 2207, at least or
exactly or at most 2208, at least or exactly or at most 2209, at
least or exactly or at most 2210, at least or exactly or at most
2211, at least or exactly or at most 2212, at least or exactly or
at most 2213, at least or exactly or at most 2214, at least or
exactly or at most 2215, at least or exactly or at most 2216, at
least or exactly or at most 2217, at least or exactly or at most
2218, at least or exactly or at most 2219, at least or exactly or
at most 2220, at least or exactly or at most 2221, at least or
exactly or at most 2222, at least or exactly or at most 2223, at
least or exactly or at most 2224, at least or exactly or at most
2225, at least or exactly or at most 2226, at least or exactly or
at most 2227, at least or exactly or at most 2228, at least or
exactly or at most 2229, at least or exactly or at most 2230, at
least or exactly or at most 2231, at least or exactly or at most
2232, at least or exactly or at most 2233, at least or exactly or
at most 2234, at least or exactly or at most 2235, at least or
exactly or at most 2236, at least or exactly or at most 2237, at
least or exactly or at most 2238, at least or exactly or at most
2239, at least or exactly or at most 2240, at least or exactly or
at most 2241, at least or exactly or at most 2242, at least or
exactly or at most 2243, at least or exactly or at most 2244, at
least or exactly or at most 2245, at least or exactly or at most
2246, at least or exactly or at most 2247, at least or exactly or
at most 2248, at least or exactly or at most 2249, at least or
exactly or at most 2250, at least or exactly or at most 2251, at
least or exactly or at most 2252, at least or exactly or at most
2253, at least or exactly or at most 2254, at least or exactly or
at most 2255, at least or exactly or at most 2256, at least or
exactly or at most 2257, at least or exactly or at most 2258, at
least or exactly or at most 2259, at least or exactly or at most
2260, at least or exactly or at most 2261, at least or exactly or
at most 2262, at least or exactly or at most 2263, at least or
exactly or at most 2264, at least or exactly or at most 2265, at
least or exactly or at most 2266, at least or exactly or at most
2267, at least or exactly or at most 2268, at least or exactly or
at most 2269, at least or exactly or at most 2270, at least or
exactly or at most 2271, at least or exactly or at most 2272, at
least or exactly or at most 2273, at least or exactly or at most
2274, at least or exactly or at most 2275, at least or exactly or
at most 2276, at least or exactly or at most 2277, at least or
exactly or at most 2278, at least or exactly or at most 2279, at
least or exactly or at most 2280, at least or exactly or at most
2281, at least or exactly or at most 2282, at least or
exactly or at most 2283, at least or exactly or at most 2284, at
least or exactly or at most 2285, at least or exactly or at most
2286, at least or exactly or at most 2287, at least or exactly or
at most 2288, at least or exactly or at most 2289, at least or
exactly or at most 2290, at least or exactly or at most 2291, at
least or exactly or at most 2292, at least or exactly or at most
2293, at least or exactly or at most 2294, at least or exactly or
at most 2295, at least or exactly or at most 2296, at least or
exactly or at most 2297, at least or exactly or at most 2298, at
least or exactly or at most 2299, at least or exactly or at most
2300, at least or exactly or at most 2301, at least or exactly or
at most 2302, at least or exactly or at most 2303, at least or
exactly or at most 2304, at least or exactly or at most 2305, at
least or exactly or at most 2306, at least or exactly or at most
2307, at least or exactly or at most 2308, at least or exactly or
at most 2309, at least or exactly or at most 2310, at least or
exactly or at most 2311, at least or exactly or at most 2312, at
least or exactly or at most 2313, at least or exactly or at most
2314, at least or exactly or at most 2315, at least or exactly or
at most 2316, at least or exactly or at most 2317, at least or
exactly or at most 2318, at least or exactly or at most 2319, at
least or exactly or at most 2320, at least or exactly or at most
2321, at least or exactly or at most 2322, at least or exactly or
at most 2323, at least or exactly or at most 2324, at least or
exactly or at most 2325, at least or exactly or at most 2326, at
least or exactly or at most 2327, at least or exactly or at most
2328, at least or exactly or at most 2329, at least or exactly or
at most 2330, at least or exactly or at most 2331, at least or
exactly or at most 2332, at least or exactly or at most 2333, at
least or exactly or at most 2334, at least or exactly or at most
2335, at least or exactly or at most 2336, at least or exactly or
at most 2337, at least or exactly or at most 2338, at least or
exactly or at most 2339, at least or exactly or at most 2340, at
least or exactly or at most 2341, at least or exactly or at most
2342, at least or exactly or at most 2343, at least or exactly or
at most 2344, at least or exactly or at most 2345, at least or
exactly or at most 2346, at least or exactly or at most 2347, at
least or exactly or at most 2348, at least or exactly or at most
2349, at least or exactly or at most 2350, at least or exactly or
at most 2351, at least or exactly or at most 2352, at least or
exactly or at most 2353, at least or exactly or at most 2354, at
least or exactly or at most 2355, at least or exactly or at most
2356, at least or exactly or at most 2357, at least or exactly or
at most 2358, at least or exactly or at most 2359, at least or
exactly or at most 2360, at least or exactly or at most 2361, at
least or exactly or at most 2362, at least or exactly or at most
2363, at least or exactly or at most 2364, at least or exactly or
at most 2365, at least or exactly or at most 2366, at least or
exactly or at most 2367, at least or exactly or at most 2368, at
least or exactly or at most 2369, at least or exactly or at most
2370, at least or exactly or at most 2371, at least or exactly or
at most 2372, at least or exactly or at most 2373, at least or
exactly or at most 2374, at least or exactly or at most 2375, at
least or exactly or at most 2376, at least or exactly or at most
2377, at least or exactly or at most 2378, at least or exactly or
at most 2379, at least or exactly or at most 2380, at least or
exactly or at most 2381, at least or exactly or at most 2382, at
least or exactly or at most 2383, at least or exactly or at most
2384, at least or exactly or at most 2385, at least or exactly or
at most 2386, at least or exactly or at most 2387, at least or
exactly or at most 2388, at least or exactly or at most 2389, at
least or exactly or at most 2390, at least or exactly or at most
2391, at least or exactly or at most 2392, at least or exactly or
at most 2393, at least or exactly or at most 2394, at least or
exactly or at most 2395, at least or exactly or at most 2396, at
least or exactly or at most 2397, at least or exactly or at most
2398, at least or exactly or at most 2399, at least or exactly or
at most 2400, at least or exactly or at most 2401, at least or
exactly or at most 2402, at least or exactly or at most 2403, at
least or exactly or at most 2404, at least or exactly or at most
2405, at least or exactly or at most 2406, at least or exactly or
at most 2407, at least or exactly or at most 2408, at least or
exactly or at most 2409, at least or exactly or at most 2410, at
least or exactly or at most 2411, at least or exactly or at most
2412, at least or exactly or at most 2413, at least or exactly or
at most 2414, at least or exactly or at most 2415, at least or
exactly or at most 2416, at least or exactly or at most 2417, at
least or exactly or at most 2418, at least or exactly or at most
2419, at least or exactly or at most 2420, at least or exactly or
at most 2421, at least or exactly or at most 2422, at least or
exactly or at most 2423, at least or exactly or at most 2424, at
least or exactly or at most 2425, at least or exactly or at most
2426, at least or exactly or at most 2427, at least or exactly or
at most 2428, at least or exactly or at most 2429, at least or
exactly or at most 2430, at least or exactly or at most 2431, at
least or exactly or at most 2432, at least or exactly or at most
2433, at least or exactly or at most 2434, at least or exactly or
at most 2435, at least or exactly or at most 2436, at least or
exactly or at most 2437, at least or exactly or at most 2438, at
least or exactly or at most 2439, at least or exactly or at most
2440, at least or exactly or at most 2441, at least or exactly or
at most 2442, at least or exactly or at most 2443, at least or
exactly or at most 2444, at least or exactly or at most 2445, at
least or exactly or at most 2446, at least or exactly or at most
2447, at least or exactly or at most 2448, at least or exactly or
at most 2449, at least or exactly or at most 2450, at least or
exactly or at most 2451, at least or exactly or at most 2452, at
least or exactly or at most 2453, at least or exactly or at most
2454, at least or exactly or at most 2455, at least or exactly or
at most 2456, at least or exactly or at most 2457, at least or
exactly or at most 2458, at least or exactly or at most 2459, at
least or exactly or at most 2460, at least or exactly or at most
2461, at least or exactly or at most 2462, at least or exactly or
at most 2463, at least or exactly or at most 2464, at least or
exactly or at most 2465, at least or exactly or at most 2466, at
least or exactly or at most 2467, at least or exactly or at most
2468, at least or exactly or at most 2469, at least or exactly or
at most 2470, at least or exactly or at most 2471, at least or
exactly or at most 2472, at least or exactly or at most 2473, at
least or exactly or at most 2474, at least or exactly or at most
2475, at least or exactly or at most 2476, at least or exactly or
at most 2477, at least or exactly or at most 2478, at least or
exactly or at most 2479, at least or exactly or at most 2480, at
least or exactly or at most 2481, at least or exactly or at most
2482, at least or exactly or at most 2483, at least or exactly or
at most 2484, at least or exactly or at most 2485, at least or
exactly or at most 2486, at least or exactly or at most 2487, at
least or exactly or at most 2488, at least or exactly or at most
2489, at least or exactly or at most 2490, at least or exactly or
at most 2491, at least or exactly or at most 2492, at least or
exactly or at most 2493, at least or exactly or at most 2494, at
least or exactly or at most 2495, at least or exactly or at most
2496, at least or exactly or at most 2497, at least or exactly or
at most 2498, at least or exactly or at most 2499, at least or
exactly or at most 2500, at least or exactly or at most 2501, at
least or exactly or at most 2502, at least or exactly or at most
2503, at least or exactly or at most 2504, at least or exactly or
at most 2505, at least or exactly or at most 2506, at least or
exactly or at most 2507, at least or exactly or at most 2508, at
least or exactly or at most 2509, at least or exactly or at most
2510, at least or exactly or at most 2511, at least or exactly or
at most 2512, at least or exactly or at most 2513, at least or
exactly or at most 2514, at least or exactly or at most 2515, at
least or exactly or at most 2516, at least or exactly or at most
2517, at least or exactly or at most 2518, at least or exactly or
at most 2519, at least or exactly or at most 2520, at least or
exactly or at most 2521, at least or exactly or at most 2522, at
least or exactly or at most 2523, at least or exactly or at most
2524, at least or exactly or at most 2525, at least or exactly or
at most 2526, at least or exactly or at most 2527, at least or
exactly or at most 2528, at least or exactly or at most 2529, at
least or exactly or at most 2530, at least or exactly or at most
2531, at least or exactly or at most 2532, at least or exactly or
at most 2533, at least or exactly or at most 2534, at least or
exactly or at most 2535, at least or exactly or at most 2536, at
least or exactly or at most 2537, at least or exactly or at most
2538, at least or exactly or at most 2539, at least or exactly or
at most 2540, at least or exactly or at most 2541, at least or
exactly or at most 2542, at least or exactly or at most 2543, at
least or exactly or at most 2544, at least or exactly or at most
2545, at least or exactly or at most 2546, at least or exactly or
at most 2547, at least or exactly or at most 2548, at least or
exactly or at most 2549, at least or exactly or at most 2550, at
least or exactly or at most 2551, at least or exactly or at most
2552, at least or exactly or at most 2553, at least or exactly or
at most 2554, at least or exactly or at most 2555, at least or
exactly or at most 2556, at least or exactly or at most 2557, at
least or exactly or at most 2558, at least or exactly or at most
2559, at least or exactly or at most 2560, at least or exactly or
at most 2561, at least or exactly or at most 2562, at least or
exactly or at most 2563, at least or exactly or at most 2564, at
least or exactly or at most 2565, at least or exactly or at most
2566, at least or exactly or at most 2567, at least or exactly or
at most 2568, at least or exactly or at most 2569, at least or
exactly or at most 2570, at least or exactly or at most 2571, at
least or exactly or at most 2572, at least or exactly or at most
2573, at least or exactly or at most 2574, at least or exactly or
at most 2575, at least or exactly or at most 2576, at least or
exactly or at most 2577, at least or exactly or at most 2578, at
least or exactly or at most 2579, at least or exactly or at most
2580, at least or exactly or at most 2581, at least or exactly or
at most 2582, at least or exactly or at most 2583, at least or
exactly or at most 2584, at least or exactly or at most 2585, at
least or exactly or at most 2586, at least or exactly or at most
2587, at least or exactly or at most 2588, at least or exactly or
at most 2589, at least or exactly or at most 2590, at least or
exactly or at most 2591, at least or exactly or at most 2592, at
least or exactly or at most 2593, at least or exactly or at most
2594, at least or exactly or at most 2595, at least or exactly or
at most 2596, at least or exactly or at most 2597, at least or
exactly or at most 2598, at least or exactly or at most 2599, at
least or exactly or at most 2600, at least or exactly or at most
2601, at least or exactly or at most 2602, at least or exactly or
at most 2603, at least or exactly or at most 2604, at least or
exactly or at most 2605, at least or exactly or at most 2606, at
least or exactly or at most 2607, at least or exactly or at most
2608, at least or exactly or at most 2609, at least or exactly or
at most 2610, at least or exactly or at most 2611, at least or
exactly or at most 2612, at least or exactly or at most 2613, at
least or exactly or at most 2614, at least or exactly or at most
2615, at least or exactly or at most 2616, at least or exactly or
at most 2617, at least or exactly or at most 2618, at least or
exactly or at most 2619, at least or exactly or at most 2620, at
least or exactly or at most 2621, at least or exactly or at most
2622, at least or exactly or at most 2623, at least or exactly or
at most 2624, at least or exactly or at most 2625, at least or
exactly or at most 2626, at least or exactly or at most 2627, at
least or exactly or at most 2628, at least or exactly or at most
2629, at least or exactly or at most 2630, at least or exactly or
at most 2631, at least or exactly or at most 2632, at least or
exactly or at most 2633, at least or exactly or at most 2634, at
least or exactly or at most 2635, at least or exactly or at most
2636, at least or exactly or at most 2637, at least or exactly or
at most 2638, at least or exactly or at most 2639, at least or
exactly or at most 2640, at least or exactly or at most 2641, at
least or exactly or at most 2642, at least or exactly or at most
2643, at least or exactly or at most 2644, at least or exactly or
at most 2645, at least or exactly or at most 2646, at least or
exactly or at most 2647, at least or exactly or at most 2648, at
least or exactly or at most 2649, at least or exactly or at most
2650, at least or exactly or at most 2651, at least or exactly or
at most 2652, at least or exactly or at most 2653, at least or
exactly or at most 2654, at least or exactly or at most 2655, at
least or exactly or at most 2656, at least or exactly or at most
2657, at least or exactly or at most 2658, at least or exactly or
at most 2659, at least or exactly or at most 2660, at least or
exactly or at most 2661, at least or exactly or at most 2662, at
least or exactly or at most 2663, at least or exactly or at most
2664, at least or exactly or at most 2665, at least or exactly or
at most 2666, at least or exactly or at most 2667, at least or
exactly or at most 2668, at least or exactly or at most 2669, at
least or exactly or at most 2670, at least or exactly or at most
2671, at least or exactly or at most 2672, at least or exactly or
at most 2673, at least or exactly or at most 2674, at least or
exactly or at most 2675, at least or exactly or at most 2676, at
least or exactly or at most 2677, at least or exactly or at most
2678, at least or exactly or at most 2679, at least or exactly or
at most 2680, at least or exactly or at most 2681, at least or
exactly or at most 2682, at least or exactly or at most 2683, at
least or exactly or at most 2684, at least or exactly or at most
2685, at least or exactly or at most 2686, at least or exactly or
at most 2687, at least or exactly or at most 2688, at least or
exactly or at most 2689, at least or exactly or at most 2690, at
least or exactly or at most 2691, at least or exactly or at most
2692, at least or exactly or at most 2693, at least or exactly or
at most 2694, at least or exactly or at most 2695, at least or
exactly or at most 2696, at least or exactly or at most 2697, at
least or exactly or at most 2698, at least or exactly or at most
2699, at least or exactly or at most 2700, at least or exactly or
at most 2701, at least or exactly or at most 2702, at least or
exactly or at most 2703, at least or exactly or at most 2704, at
least or exactly or at most 2705, at least or exactly or at most
2706, at least or exactly or at most 2707, at least or exactly or
at most 2708, at least or exactly or at most 2709, at least or
exactly or at most 2710, at least or exactly or at most 2711, at
least or exactly or at most 2712, at least or exactly or at most
2713, at least or exactly or at most 2714, at least or exactly or
at most 2715, at least or exactly or at most 2716, at least or
exactly or at most 2717, at least or exactly or at most 2718, at
least or exactly or at most 2719, at least or exactly or at most
2720, at least or exactly or at most 2721, at least or exactly or
at most 2722, at least or exactly or at most 2723, at least or
exactly or at most 2724, at least or exactly or at most 2725, at
least or exactly or at most 2726, at least or exactly or at most
2727, at least or exactly or at most 2728, at least or exactly or
at most 2729, at least or exactly or at most 2730, at least or
exactly or at most 2731, at least or exactly or at most 2732, at
least or exactly or at most 2733, at least or exactly or at most
2734, at least or exactly or at most 2735, at least or exactly or
at most 2736, at least or exactly or at most 2737, at least or
exactly or at most 2738, at least or exactly or at most 2739, at
least or exactly or at most 2740, at least or exactly or at most
2741, at least or exactly or at most 2742, at least or exactly or
at most 2743, at least or exactly or at most 2744, at least or
exactly or at most 2745, at least or exactly or at most 2746, at
least or exactly or at most 2747, at least or exactly or at most
2748, at least or exactly or at most 2749, at least or exactly or
at most 2750, at least or exactly or at most 2751, at least or
exactly or at most 2752, at least or exactly or at most 2753, at
least or exactly or at most 2754, at least or exactly or at most
2755, at least or exactly or at most 2756, at least or exactly or
at most 2757, at least or exactly or at most 2758, at least or
exactly or at most 2759, at least or exactly or at most 2760, at
least or exactly or at most 2761, at least or exactly or at most
2762, at least or exactly or at most 2763, at least or exactly or
at most 2764, at least or exactly or at most 2765, at least or
exactly or at most 2766, at least or exactly or at most 2767, at
least or exactly or at most 2768, at least or exactly or at most
2769, at least or exactly or at most 2770, at least or exactly or
at most 2771, at least or exactly or at most 2772, at least or
exactly or at most 2773, at least or exactly or at most 2774, at
least or exactly or at most 2775, at least or exactly or at most
2776, at least or exactly or at most 2777, at least or exactly or
at most 2778, at least or exactly or at most 2779, at least or
exactly or at most 2780, at least or exactly or at most 2781, at
least or exactly or at most 2782, at least or exactly or at most
2783, at least or exactly or at most 2784, at least or
exactly or at most 2785, at least or exactly or at most 2786, at
least or exactly or at most 2787, at least or exactly or at most
2788, at least or exactly or at most 2789, at least or exactly or
at most 2790, at least or exactly or at most 2791, at least or
exactly or at most 2792, at least or exactly or at most 2793, at
least or exactly or at most 2794, at least or exactly or at most
2795, at least or exactly or at most 2796, at least or exactly or
at most 2797, at least or exactly or at most 2798, at least or
exactly or at most 2799, at least or exactly or at most 2800, at
least or exactly or at most 2801, at least or exactly or at most
2802, at least or exactly or at most 2803, at least or exactly or
at most 2804, at least or exactly or at most 2805, at least or
exactly or at most 2806, at least or exactly or at most 2807, at
least or exactly or at most 2808, at least or exactly or at most
2809, at least or exactly or at most 2810, at least or exactly or
at most 2811, at least or exactly or at most 2812, at least or
exactly or at most 2813, at least or exactly or at most 2814, at
least or exactly or at most 2815, at least or exactly or at most
2816, at least or exactly or at most 2817, at least or exactly or
at most 2818, at least or exactly or at most 2819, at least or
exactly or at most 2820, at least or exactly or at most 2821, at
least or exactly or at most 2822, at least or exactly or at most
2823, at least or exactly or at most 2824, at least or exactly or
at most 2825, at least or exactly or at most 2826, at least or
exactly or at most 2827, at least or exactly or at most 2828, at
least or exactly or at most 2829, at least or exactly or at most
2830, at least or exactly or at most 2831, at least or exactly or
at most 2832, at least or exactly or at most 2833, at least or
exactly or at most 2834, at least or exactly or at most 2835, at
least or exactly or at most 2836, at least or exactly or at most
2837, at least or exactly or at most 2838, at least or exactly or
at most 2839, at least or exactly or at most 2840, at least or
exactly or at most 2841, at least or exactly or at most 2842, at
least or exactly or at most 2843, at least or exactly or at most
2844, at least or exactly or at most 2845, at least or exactly or
at most 2846, at least or exactly or at most 2847, at least or
exactly or at most 2848, at least or exactly or at most 2849, at
least or exactly or at most 2850, at least or exactly or at most
2851, at least or exactly or at most 2852, at least or exactly or
at most 2853, at least or exactly or at most 2854, at least or
exactly or at most 2855, at least or exactly or at most 2856, at
least or exactly or at most 2857, at least or exactly or at most
2858, at least or exactly or at most 2859, at least or exactly or
at most 2860, at least or exactly or at most 2861, at least or
exactly or at most 2862, at least or exactly or at most 2863, at
least or exactly or at most 2864, at least or exactly or at most
2865, at least or exactly or at most 2866, at least or exactly or
at most 2867, at least or exactly or at most 2868, at least or
exactly or at most 2869, at least or exactly or at most 2870, at
least or exactly or at most 2871, at least or exactly or at most
2872, at least or exactly or at most 2873, at least or exactly or
at most 2874, at least or exactly or at most 2875, at least or
exactly or at most 2876, at least or exactly or at most 2877, at
least or exactly or at most 2878, at least or exactly or at most
2879, at least or exactly or at most 2880, at least or exactly or
at most 2881, at least or exactly or at most 2882, at least or
exactly or at most 2883, at least or exactly or at most 2884, at
least or exactly or at most 2885, at least or exactly or at most
2886, at least or exactly or at most 2887, at least or exactly or
at most 2888, at least or exactly or at most 2889, at least or
exactly or at most 2890, at least or exactly or at most 2891, at
least or exactly or at most 2892, at least or exactly or at most
2893, at least or exactly or at most 2894, at least or exactly or
at most 2895, at least or exactly or at most 2896, at least or
exactly or at most 2897, at least or exactly or at most 2898, at
least or exactly or at most 2899, at least or exactly or at most
2900, at least or exactly or at most 2901, at least or exactly or
at most 2902, at least or exactly or at most 2903, at least or
exactly or at most 2904, at least or exactly or at most 2905, at
least or exactly or at most 2906, at least or exactly or at most
2907, at least or exactly or at most 2908, at least or exactly or
at most 2909, at least or exactly or at most 2910, at least or
exactly or at most 2911, at least or exactly or at most 2912, at
least or exactly or at most 2913, at least or exactly or at most
2914, at least or exactly or at most 2915, at least or exactly or
at most 2916, at least or exactly or at most 2917, at least or
exactly or at most 2918, at least or exactly or at most 2919, at
least or exactly or at most 2920, at least or exactly or at most
2921, at least or exactly or at most 2922, at least or exactly or
at most 2923, at least or exactly or at most 2924, at least or
exactly or at most 2925, at least or exactly or at most 2926, at
least or exactly or at most 2927, at least or exactly or at most
2928, at least or exactly or at most 2929, at least or exactly or
at most 2930, at least or exactly or at most 2931, at least or
exactly or at most 2932, at least or exactly or at most 2933, at
least or exactly or at most 2934, at least or exactly or at most
2935, at least or exactly or at most 2936, at least or exactly or
at most 2937, at least or exactly or at most 2938, at least or
exactly or at most 2939, at least or exactly or at most 2940, at
least or exactly or at most 2941, at least or exactly or at most
2942, at least or exactly or at most 2943, at least or exactly or
at most 2944, at least or exactly or at most 2945, at least or
exactly or at most 2946, at least or exactly or at most 2947, at
least or exactly or at most 2948, at least or exactly or at most
2949, at least or exactly or at most 2950, at least or exactly or
at most 2951, at least or exactly or at most 2952, at least or
exactly or at most 2953, at least or exactly or at most 2954, at
least or exactly or at most 2955, at least or exactly or at most
2956, at least or exactly or at most 2957, at least or exactly or
at most 2958, at least or exactly or at most 2959, at least or
exactly or at most 2960, at least or exactly or at most 2961, at
least or exactly or at most 2962, at least or exactly or at most
2963, at least or exactly or at most 2964, at least or exactly or
at most 2965, at least or exactly or at most 2966, at least or
exactly or at most 2967, at least or exactly or at most 2968, at
least or exactly or at most 2969, at least or exactly or at most
2970, at least or exactly or at most 2971, at least or exactly or
at most 2972, at least or exactly or at most 2973, at least or
exactly or at most 2974, at least or exactly or at most 2975, at
least or exactly or at most 2976, at least or exactly or at most
2977, at least or exactly or at most 2978, at least or exactly or
at most 2979, at least or exactly or at most 2980, at least or
exactly or at most 2981, at least or exactly or at most 2982, at
least or exactly or at most 2983, at least or exactly or at most
2984, at least or exactly or at most 2985, at least or exactly or
at most 2986, at least or exactly or at most 2987, at least or
exactly or at most 2988, at least or exactly or at most 2989, at
least or exactly or at most 2990, at least or exactly or at most
2991, at least or exactly or at most 2992, at least or exactly or
at most 2993, at least or exactly or at most 2994, at least or
exactly or at most 2995, at least or exactly or at most 2996, at
least or exactly or at most 2997, at least or exactly or at most
2998, at least or exactly or at most 2999, at least or exactly or
at most 3000, at least or exactly or at most 3001, at least or
exactly or at most 3002, at least or exactly or at most 3003, at
least or exactly or at most 3004, at least or exactly or at most
3005, at least or exactly or at most 3006, at least or exactly or
at most 3007, at least or exactly or at most 3008, at least or
exactly or at most 3009, at least or exactly or at most 3010, at
least or exactly or at most 3011, at least or exactly or at most
3012, at least or exactly or at most 3013, at least or exactly or
at most 3014, at least or exactly or at most 3015, at least or
exactly or at most 3016, at least or exactly or at most 3017, at
least or exactly or at most 3018, at least or exactly or at most
3019, at least or exactly or at most 3020, at least or exactly or
at most 3021, at least or exactly or at most 3022, at least or
exactly or at most 3023, at least or exactly or at most 3024, at
least or exactly or at most 3025, at least or exactly or at most
3026, at least or exactly or at most 3027, at least or exactly or
at most 3028, at least or exactly or at most 3029, at least or
exactly or at most 3030, at least or exactly or at most 3031, at
least or exactly or at most 3032, at least or exactly or at most
3033, at least or exactly or at most 3034, at least or exactly or
at most 3035, at least or exactly or at most 3036, at least or
exactly or at most 3037, at least or exactly or at most 3038, at
least or exactly or at most 3039, at least or exactly or at most
3040, at least or exactly or at most 3041, at least or exactly or
at most 3042, at least or exactly or at most 3043, at least or
exactly or at most 3044, at least or exactly or at most 3045, at
least or exactly or at most 3046, at least or exactly or at most
3047 contiguous amino acid residues.
[0078] In some embodiments, the polypeptide of the invention also
has a sequence identity with the amino acid sequence of a) defined
above of at least 65%, such as at least 70%, at least 75%, at least
80%, at least 85%, at least 90%, at least 91%, at least 92%, at
least 93%, at least 94%, at least 95%, at least 96%, at least 97%,
at least 98%, and at least 99%. Similarly, the polypeptide of the
invention in some embodiments also has a sequence identity with the
amino acid sequence of b) defined above of at least 60%, such as at
least 65%, at least 70%, at least 75%, at least 80%, at least 85%,
at least 90%, at least 91%, at least 92%, at least 93%, at least
94%, at least 95%, at least 96%, at least 97%, at least 98%, and at
least 99%.
[0079] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14,
15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31,
32, 33, 34, 35, 36, 37 38, 39, 40, 42, 43, 44, 45, 46, 47, 48, 49,
50, 51, 52, 53, 54, 55, and 56 in any one of SEQ ID NOs: 1-30, if
the length of the at least 5 amino acid residues so permit--if the
length of the at least 5 amino acids are higher than 5, the
N-terminal first residue will not be higher numbered than N-L+1,
where N is the number of amino acid residues of the reference
sequence and L is the number of amino acids defined for option
b.
[0080] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 57, 58, 59, 60, 61 and 62 in any on of SEQ ID
NOs: 2-30, if the length of the at least 5 amino acid residues so
permit--if the length of the at least 5 amino acids are higher than
5, the N-terminal first residue will not be higher numbered than
N-L+1, where N is the number of amino acid residues of the
reference sequence and L is the number of amino acids defined for
option b.
[0081] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 63, 64, 65, 66, 67, 68, and 69 in any one of
SEQ ID NOs: 4-30, if the length of the at least 5 amino acid
residues so permit--if the length of the at least 5 amino acids are
higher than 5, the N-terminal first residue will not be higher
numbered than N-L+1, where N is the number of amino acid residues
of the reference sequence and L is the number of amino acids
defined for option b.
[0082] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81,
82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98,
99, 100, 101, 102, 103, and 104 in any one of SEQ ID NOs: 5-30, if
the length of the at least 5 amino acid residues so permit--if the
length of the at least 5 amino acids are higher than 5, the
N-terminal first residue will not be higher numbered than N-L+1,
where N is the number of amino acid residues of the reference
sequence and L is the number of amino acids defined for option
b.
[0083] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 105, 106, 107, 108, 109, 110, and 110 in any
one of SEQ ID NOs: 6-30, if the length of the at least 5 amino acid
residues so permit--if the length of the at least 5 amino acids are
higher than 5, the N-terminal first residue will not be higher
numbered than N-L+1, where N is the number of amino acid residues
of the reference sequence and L is the number of amino acids
defined for option b.
[0084] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 111, 112, 113, 114, 115, 116, 117, 118, 119,
120, 121, and 122 in any one of SEQ ID NOs: 7-30, if the length of
the at least 5 amino acid residues so permit--if the length of the
at least 5 amino acids are higher than 5, the N-terminal first
residue will not be higher numbered than N-L+1, where N is the
number of amino acid residues of the reference sequence and L is
the number of amino acids defined for option b.
[0085] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 123, 124, 125, 126, 127, 128, 129, 130, 131,
132, 133, 134, and 135 in any one of SEQ ID NOs: 8-30, if the
length of the at least 5 amino acid residues so permit--if the
length of the at least 5 amino acids are higher than 5, the
N-terminal first residue will not be higher numbered than N-L+1,
where N is the number of amino acid residues of the reference
sequence and L is the number of amino acids defined for option
b.
[0086] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 136, 137, 138, 139, 140, 141, 142, 143, 144,
145, 146, 147, 148, 149, 150, 151, 152, 153, 154, and 155 in any
one of SEQ ID NOs: 9-30, if the length of the at least 5 amino acid
residues so permit--if the length of the at least 5 amino acids are
higher than 5, the N-terminal first residue will not be higher
numbered than N-L+1, where N is the number of amino acid residues
of the reference sequence and L is the number of amino acids
defined for option b.
[0087] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 156, 157, and 158 in any one of SEQ ID NOs:
10-30, if the length of the at least 5 amino acid residues so
permit--if the length of the at least 5 amino acids are higher than
5, the N-terminal first residue will not be higher numbered than
N-L+1, where N is the number of amino acid residues of the
reference sequence and L is the number of amino acids defined for
option b.
[0088] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 159, 160, 161, and 162 in any one of SEQ ID
NOs: 11-30, if the length of the at least 5 amino acid residues so
permit--if the length of the at least 5 amino acids are higher than
5, the N-terminal first residue will not be higher numbered than
N-L+1, where N is the number of amino acid residues of the
reference sequence and L is the number of amino acids defined for
option b.
[0089] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 163, 164, 165, 166, 167, 168, 169, 170, 171,
172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184,
185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197,
198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210,
211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223,
224, 225, and 226 in any one of SEQ ID NOs: 12-30, if the length of
the at least 5 amino acid residues so permit--if the length of the
at least 5 amino acids are higher than 5, the N-terminal first
residue will not be higher numbered than N-L+1, where N is the
number of amino acid residues of the reference sequence and L is
the number of amino acids defined for option b.
[0090] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 227, 228, 229, 230, 231, 232, 233, and 234 in
any one of SEQ ID NOs: 13-30, if the length of the at least 5 amino
acid residues so permit--if the length of the at least 5 amino
acids are higher than 5, the N-terminal first residue will not be
higher numbered than N-L+1, where N is the number of amino acid
residues of the reference sequence and L is the number of amino
acids defined for option b.
[0091] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 235, 236, 237, 238, 239, 240, 241, 242, 243,
244, 245, 246, 247, 248, and 249 in SEQ ID NOs: 14-30, if the
length of the at least 5 amino acid residues so permit--if the
length of the at least 5 amino acids are higher than 5, the
N-terminal first residue will not be higher numbered than N-L+1,
where N is the number of amino acid residues of the reference
sequence and L is the number of amino acids defined for option
b.
[0092] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 250, 251, 252, 253, 254, 255, 256, 257, 258,
259, 260, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281,
282, 283, 284, 285, 286, 287, 288, 289, and 290 in any one of SEQ
ID NOs: 15-30, if the length of the at least 5 amino acid residues
so permit--if the length of the at least 5 amino acids are higher
than 5, the N-terminal first residue will not be higher numbered
than N-L+1, where N is the number of amino acid residues of the
reference sequence and L is the number of amino acids defined for
option b.
[0093] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 291, 292, 293, 294, 295, 296, 297, 298, 299,
300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310, 311, 312,
313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324, 325,
326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338,
339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351,
and 352 in any one of SEQ ID NOs: 16-30, if the length of the at
least 5 amino acid residues so permit--if the length of the at
least 5 amino acids are higher than 5, the N-terminal first residue
will not be higher numbered than N-L+1, where N is the number of
amino acid residues of the reference sequence and L is the number
of amino acids defined for option b.
[0094] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues In the embodiments defined by option b) above,
the polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 353, 354, 355, 356, 357, 358, 359, 360, 361,
362, and 363 in any one of SEQ ID NOs: 17-30, if the length of the
at least 5 amino acid residues so permit--if the length of the at
least 5 amino acids are higher than 5, the N-terminal first residue
will not be higher numbered than N-L+1, where N is the number of
amino acid residues of the reference sequence and L is the number
of amino acids defined for option b.
[0095] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues In the embodiments defined by option b) above,
the polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 364, 365, 366, 367, 368, 369, 370, 371, 372,
373, 374, 375, 376, 377, 378, 379, 380, 381, 382, 383, 384, 385,
386, 387, 388, 389, 390, 391, 392, 393, 394, 395, 396, 397, 398,
399, 400, 401, 402, 403, 404, 405, 406, 407, 408, 409, 410, 411,
412, 413, 414, 415, and 416 in any one of SEQ ID NOs: 18-30, if the
length of the at least 5 amino acid residues so permit--if the
length of the at least 5 amino acids are higher than 5, the
N-terminal first residue will not be higher numbered than N-L+1,
where N is the number of amino acid residues of the reference
sequence and L is the number of amino acids defined for option
b.
[0096] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues In the embodiments defined by option b) above,
the polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 417, 418, 419, 420, 421, 422, 423, 424, 425,
426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436, 437, 438,
439, 440, and 441 in any one of SEQ ID NOs: 19-30, if the length of
the at least 5 amino acid residues so permit--if the length of the
at least 5 amino acids are higher than 5, the N-terminal first
residue will not be higher numbered than N-L+1, where N is the
number of amino acid residues of the reference sequence and L is
the number of amino acids defined for option b.
[0097] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues In the embodiments defined by option b) above,
the polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 442, 443, 444, 445, 446, 447, 448, 449, 450,
451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463,
464, 465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476,
477, 478, 479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489,
490, 491, 492, 493, 494, 495, 496, 497, 498, 499, 500, 501, 502,
503, 504, 505, 506, 507, 508, 509, 510, 511, 512, 513, 514, 515,
516, 517, 518, 519, 520, 521, 522, 523, 524, 525, 526, 527, 528,
529, 530, 531, 532, 533, 534, 535, 536, 537, 538, 539, 540, 541,
542, 543, 544, 545, 546, 547, 548, 549, 550, 551, 552, 553, 554,
555, 556, 557, 558, 559, 560, 561, 562, 563, 564, 565, 566, 567,
568, 569, 570, 571, 572, 573, 574, 575, 576, 577, 578, 579, 580,
581, 582, 583, 584, 585, 586, 587, 588, 589, 590, 591, 592, 593,
594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604, 605, 606,
607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618, 619,
620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632,
633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645,
646, 647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658,
659, 660, 661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671,
672, 673, 674, 675, 676, 677, 678, 679, 680, 681, 682, 683, 684,
685, 686, 687, 688, 689, 690, 691, 692, 693, 694, 695, 696, 697,
698, 699, 700, 701, 702, 703, 704, 705, 706, and 707 in any one of
SEQ ID NOs: 20-30, if the length of the at least 5 amino acid
residues so permit--if the length of the at least 5 amino acids are
higher than 5, the N-terminal first residue will not be higher
numbered than N-L+1, where N is the number of amino acid residues
of the reference sequence and L is the number of amino acids
defined for option b.
[0098] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues In the embodiments defined by option b) above,
the polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 708, 709, 710, 711, 712, 713, 714, 715, 716,
717, 718, 719, 720, 721, 722 and 723 in any one of SEQ ID NOs:
21-30, if the length of the at least 5 amino acid residues so
permit--if the length of the at least 5 amino acids are higher than
5, the N-terminal first residue will not be higher numbered than
N-L+1, where N is the number of amino acid residues of the
reference sequence and L is the number of amino acids defined for
option b.
[0099] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to amino acid
residue 724 in any one of SEQ ID NOs: 22-30, if the length of the
at least 5 amino acid residues so permit--if the length of the at
least 5 amino acids are higher than 5, the N-terminal first residue
will not be higher numbered than N-L+1, where N is the number of
amino acid residues of the reference sequence and L is the number
of amino acids defined for option b.
[0100] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues In the embodiments defined by option b) above,
the polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 725, 726, 727, 728, 729, 730, 731, 732, 733,
734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744, 745, 746,
747, 748, 749, and 750 in any one of SEQ ID NOs: 23-30, if the
length of the at least 5 amino acid residues so permit--if the
length of the at least 5 amino acids are higher than 5, the
N-terminal first residue will not be higher numbered than N-L+1,
where N is the number of amino acid residues of the reference
sequence and L is the number of amino acids defined for option
b.
[0101] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues In the embodiments defined by option b) above,
the polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 751, 752, 753, 754, 755, 756, 757, 758, 759,
760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 771, 772,
773, 774, 775, 776, 777, 778, 779, 780, 781, 782, 783, 784, 785,
786, 787, 788, 789, 790, 791, 792, 793, 794, 795, 796, 797, 798,
799, 800, 801, 802, 803, 804, 805, 806, 807, 808, 809, 810, 811,
812, 813, 814, 815, 816, 817, 818, 819, 820, 821, 822, 823, 824,
825, 826, 827, 828, 829, 830, 831, 832, 833, 834, 835, 836, 837,
838, 839, 840, 841, 842, 843, 844, 845, 846, 847, 848, 849, 850,
851, 852, 853, 854, 855, 856, 857, 858, 859, 860, 861, 862, 863,
864, 865, 866, 867, 868, 869, 870, 871, 872, 873, 874, 875, 876,
877, 878, 879, 880, 881, 882, 883, 884, 885, 886, 887, 888, 889,
890, 891, 892, 893, 894, 895, 896, 897, 898, 899, 900, 901, and 902
in any one of SEQ ID NOs: 24-30, if the length of the at least 5
amino acid residues so permit--if the length of the at least 5
amino acids are higher than 5, the N-terminal first residue will
not be higher numbered than N-L+1, where N is the number of amino
acid residues of the reference sequence and L is the number of
amino acids defined for option b.
[0102] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues In the embodiments defined by option b) above,
the polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 903, 904, 905, 906, 907, 908, 909, 910, 911,
912, 913, 914, 915, 916, 917, 918, 919, 920, 921, 922, 923, 924,
925, 926, 927, 928, 929, 930, 931, 932, 933, 934, 935, 936, 937,
938, 939, 940, 941, 942, 943, 944, 945, 946, 947, 948, 949, 950,
951, 952, 953, 954, 955, 956, 957, 958, 959, 960, 961, 962, 963,
964, 965, 966, 967, 968, 969, and 970 in any one of SEQ ID NOs:
25-30, if the length of the at least 5 amino acid residues so
permit--if the length of the at least 5 amino acids are higher than
5, the N-terminal first residue will not be higher numbered than
N-L+1, where N is the number of amino acid residues of the
reference sequence and L is the number of amino acids defined for
option b.
[0103] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues In the embodiments defined by option b) above,
the polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 971, 972, 973, 974, 975, 976, 977, 978, 979,
980, 981, 982, 983, 984, 985, 986, 987, 988, 989, 990, 991, 992,
993, 994, 995, 996, 997, 998, 999, 1000, 1001, 1002, 1003, 1004,
1005, 1006, 1007, 1008, 1009, 1010, 1011, 1012, 1013, 1014, 1015,
1016, 1017, 1018, 1019, 1020, 1021, 1022, 1023, 1024, 1025, 1026,
1027, 1028, 1029, 1030, 1031, 1032, 1033, 1034, 1035, 1036, 1037,
1038, 1039, 1040, 1041, 1042, 1043, 1044, 1045, 1046, 1047, 1048,
1049, 1050, 1051, 1052, 1053, 1054, 1055, 1056, 1057, 1058, 1059,
1060, 1061, 1062, 1063, 1064, 1065, 1066, and 1067 in any one of
SEQ ID NOs: 26-30, if the length of the at least 5 amino acid
residues so permit--if the length of the at least 5 amino acids are
higher than 5, the N-terminal first residue will not be higher
numbered than N-L+1, where N is the number of amino acid residues
of the reference sequence and L is the number of amino acids
defined for option b.
[0104] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues In the embodiments defined by option b) above,
the polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 1068, 1069, 1070, 1071, 1072, 1073, 1074, 1075,
1076, 1077, 1078, 1079, 1080, 1081, 1082, 1083, 1084, 1085, 1086,
1087, 1088, 1089, 1090, 1091, 1092, 1093, 1094, 1095, 1096, 1097,
1098, 1099, 1100, 1101, 1102, 1103, 1104, 1105, and 1106 in any one
of SEQ ID NOs: 27-30, if the length of the at least 5 amino acid
residues so permit--if the length of the at least 5 amino acids are
higher than 5, the N-terminal first residue will not be higher
numbered than N-L+1, where N is the number of amino acid residues
of the reference sequence and L is the number of amino acids
defined for option b.
[0105] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues In the embodiments defined by option b) above,
the polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 1107, 1108, 1109, 1110, 1111, 1112, 1113, 1114,
1115, 1116, 1117, 1118, 1119, 1120, 1121, 1122, 1123, 1124, 1125,
1126, 1127, 1128, 1129, 1130, 1131, 1132, 1133, 1134, 1135, 1136,
1137, 1138, 1139, 1140, 1141, 1142, 1143, 1144, 1145, 1146, 1147,
1148, 1149, 1150, 1151, 1152, 1153, 1154, 1155, 1156, 1157, 1158,
1159, 1160, 1161, 1162, 1163, 1164, 1165, 1166, 1167, 1168, 1169,
1170, 1171, 1172, 1173, 1174, 1175, 1176, 1177, 1178, 1179, 1180,
1181, 1182, 1183, 1184, 1185, 1186, 1187, 1188, 1189, 1190, 1191,
1192, 1193, 1194, 1195, 1196, 1197, 1198, 1199, 1200, 1201, 1202,
1203, 1204, 1205, 1206, 1207, 1208, 1209, 1210, 1211, 1212, 1213,
1214, 1215, 1216, 1217, 1218, 1219, 1220, 1221, 1222, 1223, and
1224 in any one of SEQ ID NOs: 28-30, if the length of the at least
5 amino acid residues so permit--if the length of the at least 5
amino acids are higher than 5, the N-terminal first residue will
not be higher numbered than N-L+1, where N is the number of amino
acid residues of the reference sequence and L is the number of
amino acids defined for option b.
[0106] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues In the embodiments defined by option b) above,
the polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 1225, 1226, 1227, 1228, 1229, 1230, 1231, 1232,
1233, 1234, 1235, 1236, 1237, 1238, 1239, 1240, 1241, 1242, 1243,
1244, 1245, 1246, 1247, 1248, 1249, 1250, 1251, 1252, 1253, 1254,
1255, 1256, 1257, 1258, 1259, 1260, 1261, 1262, 1263, 1264, 1265,
1266, 1267, 1268, 1269, 1270, 1271, 1272, 1273, 1274, 1275, 1276,
1277, 1278, 1279, and 1280 in any one of SEQ ID NOs: 29-30, if the
length of the at least 5 amino acid residues so permit--if the
length of the at least 5 amino acids are higher than 5, the
N-terminal first residue will not be higher numbered than N-L+1,
where N is the number of amino acid residues of the reference
sequence and L is the number of amino acids defined for option
b.
[0107] In the embodiments defined by option b) above, the
polypeptide of the invention is also one that has at least 5
contiguous amino acid residues defined for option b) above and also
has its N-terminal amino acid residue corresponding to any one of
amino acid residues 1281, 1282, 1283, 1284, 1285, 1286, 1287, 1288,
1289, 1290, 1291, 1292, 1293, 1294, 1295, 1296, 1297, 1298, 1299,
1300, 1301, 1302, 1303, 1304, 1305, 1306, 1307, 1308, 1309, 1310,
1311, 1312, 1313, 1314, 1315, 1316, 1317, 1318, 1319, 1320, 1321,
1322, 1323, 1324, 1325, 1326, 1327, 1328, 1329, 1330, 1331, 1332,
1333, 1334, 1335, 1336, 1337, 1338, 1339, 1340, 1341, 1342, 1343,
1344, 1345, 1346, 1347, 1348, 1349, 1350, 1351, 1352, 1353, 1354,
1355, 1356, 1357, 1358, 1359, 1360, 1361, 1362, 1363, 1364, 1365,
1366, 1367, 1368, 1369, 1370, 1371, 1372, 1373, 1374, 1375, 1376,
1377, 1378, 1379, 1380, 1381, 1382, 1383, 1384, 1385, 1386, 1387,
1388, 1389, 1390, 1391, 1392, 1393, 1394, 1395, 1396, 1397, 1398,
1399, 1400, 1401, 1402, 1403, 1404, 1405, 1406, 1407, 1408, 1409,
1410, 1411, 1412, 1413, 1414, 1415, 1416, 1417, 1418, 1419, 1420,
1421, 1422, 1423, 1424, 1425, 1426, 1427, 1428, 1429, 1430, 1431,
1432, 1433, 1434, 1435, 1436, 1437, 1438, 1439, 1440, 1441, 1442,
1443, 1444, 1445, 1446, 1447, 1448, 1449, 1450, 1451, 1452, 1453,
1454, 1455, 1456, 1457, 1458, 1459, 1460, 1461, 1462, 1463, 1464,
1465, 1466, 1467, 1468, 1469, 1470, 1471, 1472, 1473, 1474, 1475,
1476, 1477, 1478, 1479, 1480, 1481, 1482, 1483, 1484, 1485, 1486,
1487, 1488, 1489, 1490, 1491, 1492, 1493, 1494, 1495, 1496, 1497,
1498, 1499, 1500, 1501, 1502, 1503, 1504, 1505, 1506, 1507, 1508,
1509, 1510, 1511, 1512, 1513, 1514, 1515, 1516, 1517, 1518, 1519,
1520, 1521, 1522, 1523, 1524, 1525, 1526, 1527, 1528, 1529, 1530,
1531, 1532, 1533, 1534, 1535, 1536, 1537, 1538, 1539, 1540, 1541,
1542, 1543, 1544, 1545, 1546, 1547, 1548, 1549, 1550, 1551, 1552,
1553, 1554, 1555, 1556, 1557, 1558, 1559, 1560, 1561, 1562, 1563,
1564, 1565, 1566, 1567, 1568, 1569, 1570, 1571, 1572, 1573, 1574,
1575, 1576, 1577, 1578, 1579, 1580, 1581, 1582, 1583, 1584, 1585,
1586, 1587, 1588, 1589, 1590, 1591, 1592, 1593, 1594, 1595, 1596,
1597, 1598, 1599, 1600, 1601, 1602, 1603, 1604, 1605, 1606, 1607,
1608, 1609, 1610, 1611, 1612, 1613, 1614, 1615, 1616, 1617, 1618,
1619, 1620, 1621, 1622, 1623, 1624, 1625, 1626, 1627, 1628, 1629,
1630, 1631, 1632, 1633, 1634, 1635, 1636, 1637, 1638, 1639, 1640,
1641, 1642, 1643, 1644, 1645, 1646, 1647, 1648, 1649, 1650, 1651,
1652, 1653, 1654, 1655, 1656, 1657, 1658, 1659, 1660, 1661, 1662,
1663, 1664, 1665, 1666, 1667, 1668, 1669, 1670, 1671, 1672, 1673,
1674, 1675, 1676, 1677, 1678, 1679, 1680, 1681, 1682, 1683, 1684,
1685, 1686, 1687, 1688, 1689, 1690, 1691, 1692, 1693, 1694, 1695,
1696, 1697, 1698, 1699, 1700, 1701, 1702, 1703, 1704, 1705, 1706,
1707, 1708, 1709, 1710, 1711, 1712, 1713, 1714, 1715, 1716, 1717,
1718, 1719, 1720, 1721, 1722, 1723, 1724, 1725, 1726, 1727, 1728,
1729, 1730, 1731, 1732, 1733, 1734, 1735, 1736, 1737, 1738, 1739,
1740, 1741, 1742, 1743, 1744, 1745, 1746, 1747, 1748, 1749, 1750,
1751, 1752, 1753, 1754, 1755, 1756, 1757, 1758, 1759, 1760, 1761,
1762, 1763, 1764, 1765, 1766, 1767, 1768, 1769, 1770, 1771, 1772,
1773, 1774, 1775, 1776, 1777, 1778, 1779, 1780, 1781, 1782, 1783,
1784, 1785, 1786, 1787, 1788, 1789, 1790, 1791, 1792, 1793, 1794,
1795, 1796, 1797, 1798, 1799, 1800, 1801, 1802, 1803, 1804, 1805,
1806, 1807, 1808, 1809, 1810, 1811, 1812, 1813, 1814, 1815, 1816,
1817, 1818, 1819, 1820, 1821, 1822, 1823, 1824, 1825, 1826, 1827,
1828, 1829, 1830, 1831, 1832, 1833, 1834, 1835, 1836, 1837, 1838,
1839, 1840, 1841, 1842, 1843, 1844, 1845, 1846, 1847, 1848, 1849,
1850, 1851, 1852, 1853, 1854, 1855, 1856, 1857, 1858, 1859, 1860,
1861, 1862, 1863, 1864, 1865, 1866, 1867, 1868, 1869, 1870, 1871,
1872, 1873, 1874, 1875, 1876, 1877, 1878, 1879, 1880, 1881, 1882,
1883, 1884, 1885, 1886, 1887, 1888, 1889, 1890, 1891, 1892, 1893,
1894, 1895, 1896, 1897, 1898, 1899, 1900, 1901, 1902, 1903, 1904,
1905, 1906, 1907, 1908, 1909, 1910, 1911, 1912, 1913, 1914, 1915,
1916, 1917, 1918, 1919, 1920, 1921, 1922, 1923, 1924, 1925, 1926,
1927, 1928, 1929, 1930, 1931, 1932, 1933, 1934, 1935, 1936, 1937,
1938, 1939, 1940, 1941, 1942, 1943, 1944, 1945, 1946, 1947, 1948,
1949, 1950, 1951, 1952, 1953, 1954, 1955, 1956, 1957, 1958, 1959,
1960, 1961, 1962, 1963, 1964, 1965, 1966, 1967, 1968, 1969, 1970,
1971, 1972, 1973, 1974, 1975, 1976, 1977, 1978, 1979, 1980, 1981,
1982, 1983, 1984, 1985, 1986, 1987, 1988, 1989, 1990, 1991, 1992,
1993, 1994, 1995, 1996, 1997, 1998, 1999, 2000, 2001, 2002, 2003,
2004, 2005, 2006, 2007, 2008, 2009, 2010, 2011, 2012, 2013, 2014,
2015, 2016, 2017, 2018, 2019, 2020, 2021, 2022, 2023, 2024, 2025,
2026, 2027, 2028, 2029, 2030, 2031, 2032, 2033, 2034, 2035, 2036,
2037, 2038, 2039, 2040, 2041, 2042, 2043, 2044, 2045, 2046, 2047,
2048, 2049, 2050, 2051, 2052, 2053, 2054, 2055, 2056, 2057, 2058,
2059, 2060, 2061, 2062, 2063, 2064, 2065, 2066, 2067, 2068, 2069,
2070, 2071, 2072, 2073, 2074, 2075, 2076, 2077, 2078, 2079, 2080,
2081, 2082, 2083, 2084, 2085, 2086, 2087, 2088, 2089, 2090, 2091,
2092, 2093, 2094, 2095, 2096, 2097, 2098, 2099, 2100, 2101, 2102,
2103, 2104, 2105, 2106, 2107, 2108, 2109, 2110, 2110, 2111, 2112,
2113, 2114, 2115, 2116, 2117, 2118, 2119, 2120, 2121, 2122, 2123,
2124, 2125, 2126, 2127, 2128, 2129, 2130, 2131, 2132, 2133, 2134,
2135, 2136, 2137, 2138, 2139, 2140, 2141, 2142, 2143, 2144, 2145,
2146, 2147, 2148, 2149, 2150, 2151, 2152, 2153, 2154, 2155, 2156,
2157, 2158, 2159, 2160, 2171, 2172, 2173, 2174, 2175, 2176, 2177,
2178, 2179, 2180, 2181, 2182, 2183, 2184, 2185, 2186, 2187, 2188,
2189, 2190, 2191, 2192, 2193, 2194, 2195, 2196, 2197, 2198, 2199,
2200, 2201, 2202, 2203, 2204, 2205, 2206, 2207, 2208, 2209, 2210,
2211, 2212, 2213, 2214, 2215, 2216, 2217, 2218, 2219, 2220, 2221,
2222, 2223, 2224, 2225, 2226, 2227, 2228, 2229, 2230, 2231, 2232,
2233, 2234, 2235, 2236, 2237, 2238, 2239, 2240, 2241, 2242, 2243,
2244, 2245, 2246, 2247, 2248, 2249, 2250, 2251, 2252, 2253, 2254,
2255, 2256, 2257, 2258, 2259, 2260, 2271, 2272, 2273, 2274, 2275,
2276, 2277, 2278, 2279, 2280, 2281, 2282, 2283, 2284, 2285, 2286,
2287, 2288, 2289, 2290, 2291, 2292, 2293, 2294, 2295, 2296, 2297,
2298, 2299, 2300, 2301, 2302, 2303, 2304, 2305, 2306, 2307, 2308,
2309, 2310, 2311, 2312, 2313, 2314, 2315, 2316, 2317, 2318, 2319,
2320, 2321, 2322, 2323, 2324, 2325, 2326, 2327, 2328, 2329, 2330,
2331, 2332, 2333, 2334, 2335, 2336, 2337, 2338, 2339, 2340, 2341,
2342, 2343, 2344, 2345, 2346, 2347, 2348, 2349, 2350, 2351, 2352,
2353, 2354, 2355, 2356, 2357, 2358, 2359, 2360, 2361, 2362, 2363,
2364, 2365, 2366, 2367, 2368, 2369, 2370, 2371, 2372, 2373, 2374,
2375, 2376, 2377, 2378, 2379, 2380, 2381, 2382, 2383, 2384, 2385,
2386, 2387, 2388, 2389, 2390, 2391, 2392, 2393, 2394, 2395, 2396,
2397, 2398, 2399, 2400, 2401, 2402, 2403, 2404, 2405, 2406, 2407,
2408, 2409, 2410, 2411, 2412, 2413, 2414, 2415, 2416, 2417, 2418,
2419, 2420, 2421, 2422, 2423, 2424, 2425, 2426, 2427, 2428, 2429,
2430, 2431, 2432, 2433, 2434, 2435, 2436, 2437, 2438, 2439, 2440,
2441, 2442, 2443, 2444, 2445, 2446, 2447, 2448, 2449, 2450, 2451,
2452, 2453, 2454, 2455, 2456, 2457, 2458, 2459, 2460, 2461, 2462,
2463, 2464, 2465, 2466, 2467, 2468, 2469, 2470, 2471, 2472, 2473,
2474, 2475, 2476, 2477, 2478, 2479, 2480, 2481, 2482, 2483, 2484,
2485, 2486, 2487, 2488, 2489, 2490, 2491, 2492, 2493, 2494, 2495,
2496, 2497, 2498, 2499, 2500, 2501, 2502, 2503, 2504, 2505, 2506,
2507, 2508, 2509, 2510, 2511, 2512, 2513, 2514, 2515, 2516, 2517,
2518, 2519, 2520, 2521, 2522, 2523, 2524, 2525, 2526, 2527, 2528,
2529, 2530, 2531, 2532, 2533, 2534, 2535, 2536, 2537, 2538, 2539,
2540, 2541, 2542, 2543, 2544, 2545, 2546, 2547, 2548, 2549, 2550,
2551, 2552, 2553, 2554, 2555, 2556, 2557, 2558, 2559, 2560, 2561,
2562, 2563, 2564, 2565, 2566, 2567, 2568, 2569, 2570, 2571, 2572,
2573, 2574, 2575, 2576, 2577, 2578, 2579, 2580, 2581, 2582, 2583,
2584, 2585, 2586, 2587, 2588, 2589, 2590, 2591, 2592, 2593, 2594,
2595, 2596, 2597, 2598, 2599, 2600, 2601, 2602, 2603, 2604, 2605,
2606, 2607, 2608, 2609, 2610, 2611, 2612, 2613, 2614, 2615, 2616,
2617, 2618, 2619, 2620, 2621, 2622, 2623, 2624, 2625, 2626, 2627,
2628, 2629, 2630, 2631, 2632, 2633, 2634, 2635, 2636, 2637, 2638,
2639, 2640, 2641, 2642, 2643, 2644, 2645, 2646, 2647, 2648, 2649,
2650, 2651, 2652, 2653, 2654, 2655, 2656, 2657, 2658, 2659, 2660,
2661, 2662, 2663, 2664, 2665, 2666, 2667, 2668, 2669, 2670, 2671,
2672, 2673, 2674, 2675, 2676, 2677, 2678, 2679, 2680, 2681, 2682,
2683, 2684, 2685, 2686, 2687, 2688, 2689, 2690, 2691, 2692, 2693,
2694, 2695, 2696, 2697, 2698, 2699, 2700, 2701, 2702, 2703, 2704,
2705, 2706, 2707, 2708, 2709, 2710, 2711, 2712, 2713, 2714, 2715,
2716, 2717, 2718, 2719, 2720, 2721, 2722, 2723, 2724, 2725, 2726,
2727, 2728, 2729, 2730, 2731, 2732, 2733, 2734, 2735, 2736, 2737,
2738, 2739, 2740, 2741, 2742, 2743, 2744, 2745, 2746, 2747, 2748,
2749, 2750, 2751, 2752, 2753, 2754, 2755, 2756, 2757, 2758, 2759,
2760, 2761, 2762, 2763, 2764, 2765, 2766, 2767, 2768, 2769, 2770,
2771, 2772, 2773, 2774, 2775, 2776, 2777, 2778, 2779, 2780, 2781,
2782, 2783, 2784, 2785, 2786, 2787, 2788, 2789, 2790, 2791, 2792,
2793, 2794, 2795, 2796, 2797, 2798, 2799, 2800, 2801, 2802, 2803,
2804, 2805, 2806, 2807, 2808, 2809, 2810, 2811, 2812, 2813, 2814,
2815, 2816, 2817, 2818, 2819, 2820, 2821, 2822, 2823, 2824, 2825,
2826, 2827, 2828, 2829, 2830, 2831, 2832, 2833, 2834, 2835, 2836,
2837, 2838, 2839, 2840, 2841, 2842, 2843, 2844, 2845, 2846, 2847,
2848, 2849, 2850, 2851, 2852, 2853, 2854, 2855, 2856, 2857, 2858,
2859, 2860, 2861, 2862, 2863, 2864, 2865, 2866, 2867, 2868, 2869,
2870, 2871, 2872, 2873, 2874, 2875, 2876, 2877, 2878, 2879, 2880,
2881, 2882, 2883, 2884, 2885, 2886, 2887, 2888, 2889, 2890, 2891,
2892, 2893, 2894, 2895, 2896, 2897, 2898, 2899, 2900, 2901, 2902,
2903, 2904, 2905, 2906, 2907, 2908, 2909, 2910, 2911, 2912, 2913,
2914, 2915, 2916, 2917, 2918, 2919, 2920, 2921, 2922, 2923, 2924,
2925, 2926, 2927, 2928, 2929, 2930, 2931, 2932, 2933, 2934, 2935,
2936, 2937, 2938, 2939, 2940, 2941, 2942, 2943, 2944, 2945, 2946,
2947, 2948, 2949, 2950, 2951, 2952, 2953, 2954, 2955, 2956, 2957,
2958, 2959, 2960, 2961, 2962, 2963, 2964, 2965, 2966, 2967, 2968,
2969, 2970, 2971, 2972, 2973, 2974, 2975, 2976, 2977, 2978, 2979,
2980, 2981, 2982, 2983, 2984, 2985, 2986, 2987, 2988, 2989, 2990,
2991, 2992, 2993, 2994, 2995, 2996, 2997, 2998, 2999, 3000, 3001,
3002, 3003, 3004, 3005, 3006, 3007, 3008, 3009, 3010, 3011, 3012,
3013, 3014, 3015, 3016, 3017, 3018, 3019, 3020, 3021, 3022, 3023,
3024, 3025, 3026, 3027, 3028, 3029, 3030, 3031, 3032, 3033, 3034,
3035, 3036, 3037, 3038, 3039, 3040, 3042, and 3043 in any one of
SEQ ID NOs: 30, if the length of the at least 5 amino acid residues
so permit--if the length of the at least 5 amino acids are higher
than 5, the N-terminal first residue will not be higher numbered
than N-L+1, where N is the number of amino acid residues of the
reference sequence and L is the number of amino acids defined for
option b.
[0108] The polypeptide of the invention is in certain embodiments
also fused or conjugated to an immunogenic carrier molecule; or,
phrased otherwise, the polypeptide of the invention also includes
such an immunogenic carrier molecule in addition to the material
derived from SEQ ID NOs. 1-30. The immunogenic carrier molecule is
a typically polypeptide that induces T-helper lymphocyte responses
in a majority of humans, such as immunogenic carrier proteins
selected from the group consisting of keyhole limpet hemocyanino or
a fragment thereof, tetanus toxoid or a fragment thereof,
dipththeria toxoid or a fragment thereof. Other suitable carrier
molecules are discussed infra. One further fusion partner, which is
preferably incorporated is a "His tag", i.e. a stretch of amino
acids, which is rich or only consists of histidinyl residues so as
to facilitate protein purification.
[0109] In preferred embodiments, the polypeptide of the invention
detailed above is capable of inducing an adaptive immune response
against the polypeptide in a mammal, in particular in a human
being. Preferably, the adaptive immune response is a protective
adaptive immune response against infection with A baumanii. The
polypeptide may in these cases induce a humeral and/or a cellular
immune response.
Epitopes
[0110] SEQ ID NOs: 1-30 include antigenic determinants (epitopes)
that are as such recognized by antibodies and/or when bound to MHC
molecules by T-cell receptors. For the purposes of the present
invention, B-cell epitopes (i.e. antibody binding epitopes) are of
particular relevance.
[0111] It is relatively uncomplicated to identify linear B-cell
epitopes--one very simple approach entails that antibodies raised
against A. baumannii or A. baumannii derived proteins disclosed
herein are tested for binding to overlapping oligomeric peptides
derived from any one of SEQ ID NO: 1-30. Thereby, the regions of
the A. baumannii polypeptide which are responsible for or
contribute to binding to the antibodies can be identified.
[0112] Alternatively, or additionally, one can produce mutated
versions of the polypeptides of the invention, e.g. version where
each single non-alanine residue in SEQ ID NOs.: 1-30 are point
mutated to alanine--this method also assists in identifying complex
assembled B-cell epitopes; this is the case when binding of the
same antibody is modified by exchanging amino acids in different
areas of the full-length polypeptide.
[0113] Also, in silico methods for B-cell epitope prediction can be
employed: useful state-of-the-art systems for .beta.-turn
prediction is provided in Petersen B et al. (November 2010), Plos
One 5(11): e15079; prediction of linear B-cell epitopes, cf: Larsen
3 E P et al. (April 2006), Immunome Research, 2:2; prediction of
solvent exposed amino acids: Petersen B et al (July 2009), BMC
Structural Biology, 9:51.
The Nucleic Acid Fragments of the Invention
[0114] The nucleic acid fragment of the invention referred to above
is preferably is a DNA fragment (such as SEQ ID NOs: 31-60) or an
RNA fragment (such as SEQ ID NOs 61-90).
[0115] The nucleic acid fragment of the invention typically
consists of at least or exactly or at most 11, such as at least or
exactly or at most 12, at least or exactly or at most 13, at least
or exactly or at most 14, at least or exactly or at most 15, at
least or exactly or at most 16, at least or exactly or at most 17
at least or exactly or at most 18, at least or exactly or at most
19, at least or exactly or at most 20, at least or exactly or at
most 21, at least or exactly or at most 22, at least or exactly or
at most 23, at least or exactly or at most 24, at least or exactly
or at most 25, at least or exactly or at most 26, at least or
exactly or at most 27, at least or exactly or at most 28, at least
or exactly or at most 29, at least or exactly or at most 30, at
least or exactly or at most 31, at least or exactly or at most 32,
at least or exactly or at most 33, at least or exactly or at most
34, at least or exactly or at most 35, at least or exactly or at
most 36, at least or exactly or at most 37, at least or exactly or
at most 38, at least or exactly or at most 39, at least or exactly
or at most 40, at least or exactly or at most 41, at least or
exactly or at most 42, at least or exactly or at most 43, at least
or exactly or at most 44, at least or exactly or at most 45, at
least or exactly or at most 46, at least or exactly or at most 47,
at least or exactly or at most 48, at least or exactly or at most
49, at least or exactly or at most 50, at least or exactly or at
most 51, at least or exactly or at most 52, at least or exactly or
at most 53, at least or exactly or at most 54, at least or exactly
or at most 55, at least or exactly or at most 56, at least or
exactly or at most 57, at least or exactly or at most 58, at least
or exactly or at most 59, at least or exactly or at most 60, at
least or exactly or at most 61, at least or exactly or at most 62,
at least or exactly or at most 63, at least or exactly or at most
64, at least or exactly or at most 65, at least or exactly or at
most 66, at least or exactly or at most 67, at least or exactly or
at most 68, at least or exactly or at most 69, at least or exactly
or at most 70, at least or exactly or at most 71, at least or
exactly or at most 72, at least or exactly or at most 73, at least
or exactly or at most 74, at least or exactly or at most 75, at
least or exactly or at most 76, at least or exactly or at most 77,
at least or exactly or at most 78, at least or exactly or at most
79, at least or exactly or at most 80, at least or exactly or at
most 81, at least or exactly or at most 82, at least or exactly or
at most 83, at least or exactly or at most 84, at least or exactly
or at most 85, at least or exactly or at most 86, at least or
exactly or at most 87, at least or exactly or at most 88, at least
or exactly or at most 89, at least or exactly or at most 90, at
least or exactly or at most 91, at least or exactly or at most 92,
at least or exactly or at most 93, at least or exactly or at most
94, at least or exactly or at most 95, at least or exactly or at
most 96, at least or exactly or at most 97, at least or exactly or
at most 98, at least or exactly or at most 99, at least or exactly
or at most 100, at least or exactly or at most 101, at least or
exactly or at most 102, at least or exactly or at most 103, at
least or exactly or at most 104, at least or exactly or at most
105, at least or exactly or at most 106, at least or exactly or at
most 107, at least or exactly or at most 108, at least or exactly
or at most 109, at least or exactly or at most 110, at least or
exactly or at most 111, at least or exactly or at most 112, at
least or exactly or at most 113, at least or exactly or at most
114, at least or exactly or at most 115, at least or exactly or at
most 116, at least or exactly or at most 117, at least or exactly
or at most 118, at least or exactly or at most 119, at least or
exactly or at most 120, at least or exactly or at most 121, at
least or exactly or at most 122, at least or exactly or at most
123, at least or exactly or at most 124, at least or exactly or at
most 125, at least or exactly or at most 126, at least or exactly
or at most 127, at least or exactly or at most 128, at least or
exactly or at most 129, at least or exactly or at most 130, at
least or exactly or at most 131, at least or exactly or at most
132, at least or exactly or at most 133, at least or exactly or at
most 134, at least or exactly or at most 135, at least or exactly
or at most 136, at least or exactly or at most 137, at least or
exactly or at most 138, at least or exactly or at most 139, at
least or exactly or at most 140, at least or exactly or at most
141, at least or exactly or at most 142, at least or exactly or at
most 143, at least or exactly or at most 144, at least or exactly
or at most 145, at least or exactly or at most 146, at least or
exactly or at most 147, at least or exactly or at most 148, at
least or exactly or at most 149, at least or exactly or at most
150, at least or exactly or at most 151, at least or exactly or at
most 152, at least or exactly or at most 153, at least or exactly
or at most 154, at least or exactly or at most 155, at least or
exactly or at most 156, at least or exactly or at most 157, at
least or exactly or at most 158, at least or exactly or at most
159, at least or exactly or at most 160, at least or exactly or at
most 161, at least or exactly or at most 162, at least or exactly
or at most 163, at least or exactly or at most 164, at least or
exactly or at most 165, at least or exactly or at most 166, at
least or exactly or at most 167, at least or exactly or at most
168, at least or exactly or at most 169, at least or exactly or at
most 170, at least or exactly or at most 171, at least or exactly
or at most 172, at least or exactly or at most 173, at least or
exactly or at most 174, at least or exactly or at most 175, at
least or exactly or at most 176, at least or exactly or at most
177, at least or exactly or at most 178, at least or exactly or at
most 179, at least or exactly or at most 180, at least or exactly
or at most 181, at least or exactly or at most 182 and at least or
exactly or at most 183 consecutive nucleotides in any one of SEQ ID
NOs: 31-90. Longer fragments are contemplated, i.e. fragments
having at least or exactly or at most 200, at least or exactly or
at most 300 at least or exactly or at most 400, at least or exactly
or at most 500, at least or exactly or at most 600, at least or
exactly or at most 700, at least or exactly or at most 800, at
least or exactly or at most 900, at least or exactly or at most
1000, at least or exactly or at most 1500, at least or exactly or
at most 2000, at least or exactly or at most 2500, at least or
exactly or at most 3000, at least or exactly or at most 3500, and
at least or exactly or at most 4000 nucleotides from those of SEQ
ID NOs: 31-90 that encompass fragments of such lengths.
[0116] Particularly preferred nucleic acid fragments (DNA or RNA)
are those fragments of any one of SEQ ID NOs 31-90, which encode a
polypeptide of the present invention discussed supra.
[0117] The nucleic acid fragment of the invention discussed above
typically has a sequence identity with the nucleotide sequence
defined for i) or ii) above, which is at least 65%, such as at
least 70%, at least 75%, at least 80%, at least 85%, at least 90%,
at least 91%, at least 92%, at least 93%, at least 94%, at least
95%, at least 96%, at least 97%, at least 98%, and at least
99%.
[0118] The nucleic acid fragment of the invention discussed above
may also have a sequence identity with the nucleotide sequence
defined for iii) above, which is at least 65%, such as at least
70%, at least 75%, at least 80%, at least 85%, at least 90%, at
least 91%, at least 92%, at least 93%, at least 94%, at least 95%,
at least 96%, at least 97%, at least 98%, and at least 99%.
The Vectors of the Invention
[0119] Vectors of the invention fall into several categories
discussed infra. One preferred vector of the invention comprises in
operable linkage and in the 5'-3' direction, an expression control
region comprising an enhancer/promoter for driving expression of
the nucleic acid fragment defined for option i) above, optionally a
signal peptide coding sequence, a nucleotide sequence defined for
option i), and optionally a terminator. Hence, such a vector
constitutes an expression vector useful for effecting production in
cells of the polypeptide of the invention. Since the polypeptides
of the invention are bacterial of origin, recombinant production is
conveniently effected in bacterial host cells, so here it is
preferred that the expression control region drives expression in
prokaryotic cell such as a bacterium, e.g. in E coli. However, if
the vector is to drive expression in mammalian cell (as would be
the case for a DNA vaccine vector), the expression control region
should be adapted to this particular use.
[0120] At any rate, certain vectors of the invention are capable of
autonomous replication.
[0121] Also, the vector of the invention may be one that is capable
of being integrated into the genome of a host cell--this is
particularly useful if the vector is use in the production of
stably transformed cells, where the progeny will also include the
genetic information introduced via the vector. Alternatively,
vectors incapable of being integrated into the genome of a
mammalian host cell are useful in e.g. DNA vaccination.
[0122] Typically, the vector of the invention is selected from the
group consisting of a virus, such as a attenuated virus (which may
in itself be useful as a vaccine agent), a bacteriophage, a
plasmid, a minichromosome, and a cosmid.
[0123] A more detailed discussion of vectors of the invention is
provided in the following:
[0124] Polypeptides of the invention may be encoded by a nucleic
acid molecule comprised in a vector. A nucleic acid sequence can be
"heterologous," which means that it is in a context foreign to the
cell in which the vector is being introduced, which includes a
sequence homologous to a sequence in the cell but in a position
within the host cell where it is ordinarily not found. Vectors
include naked DNAs, RNAs, plasmids, cosmids, viruses
(bacteriophage, animal viruses, and plant viruses), and artificial
chromosomes (e.g., YACs). One of skill in the art would be well
equipped to construct a vector through standard recombinant
techniques (for example Sambrook et al, 2001; Ausubel et al, 1996,
both incorporated herein by reference). In addition to encoding the
polypeptides of this invention, a vector of the present invention
may encode polypeptide sequences such as a tag or immunogenicity
enhancing peptide (e.g. an immunogenic carrier or a fusion partner
that stimulates the immune system, such as a cytokine or active
fragment thereof). Useful vectors encoding such fusion proteins
include pIN vectors (Inouye et al, 1985), vectors encoding a
stretch of histidines, and pGEX vectors, for use in generating
glutathione S-transferase (GST) soluble fusion proteins for later
purification and separation or cleavage.
[0125] Vectors of the invention may be used in a host cell to
produce a polypeptide of the invention that may subsequently be
purified for administration to a subject or the vector may be
purified for direct administration to a subject for expression of
the protein in the subject (as is the case when administering a
nucleic acid vaccine).
[0126] Expression vectors can contain a variety of "control
sequences," which refer to nucleic acid sequences necessary for the
transcription and possibly translation of an operably linked coding
sequence in a particular host organism. In addition to control
sequences that govern transcription and translation, vectors and
expression vectors may contain nucleic acid sequences that serve
other functions as well and are described infra.
1. Promoters and Enhancers
[0127] A "promoter" is a control sequence. The promoter is
typically a region of a nucleic acid sequence at which initiation
and rate of transcription are controlled. It may contain genetic
elements at which regulatory proteins and molecules may bind such
as RNA polymerase and other transcription factors. The phrases
"operatively positioned," "operatively linked," "under control,"
and "under transcriptional control" mean that a promoter is in a
correct functional location and/or orientation in relation to a
nucleic acid sequence to control transcriptional initiation and
expression of that sequence. A promoter may or may not be used in
conjunction with an "enhancer," which refers to a cis-acting
regulatory sequence involved in the transcriptional activation of a
nucleic acid sequence.
[0128] A promoter may be one naturally associated with a gene or
sequence, as may be obtained by isolating the 5' non-coding
sequences located upstream of the coding segment or exon. Such a
promoter can be referred to as "endogenous." Similarly, an enhancer
may be one naturally associated with a nucleic acid sequence,
located either downstream or upstream of that sequence.
Alternatively, certain advantages will be gained by positioning the
coding nucleic acid segment under the control of a recombinant or
heterologous promoter, which refers to a promoter that is not
normally associated with a nucleic acid sequence in its natural
environment. A recombinant or heterologous enhancer refers also to
an enhancer not normally associated with a nucleic acid sequence in
its natural state. Such promoters or enhancers may include
promoters or enhancers of other genes, and promoters or enhancers
isolated from any other prokaryotic, viral, or eukaryotic cell, and
promoters or enhancers not "naturally occurring," i.e., containing
different elements of different transcriptional regulatory regions,
and/or mutations that alter expression. In addition to producing
nucleic acid sequences of promoters and enhancers synthetically,
sequences may be produced using recombinant cloning and/or nucleic
acid amplification technology, including PCR.TM., in connection
with the compositions disclosed herein (see U.S. Pat. No.
4,683,202, U.S. Pat. No. 5,928,906, each incorporated herein by
reference).
[0129] Naturally, it may be important to employ a promoter and/or
enhancer that effectively direct(s) the expression of the DNA
segment in the cell type or organism chosen for expression. Those
of skill in the art of molecular biology generally know the use of
promoters, enhancers, and cell type combinations for protein
expression (see Sambrook et al, 2001, incorporated herein by
reference). The promoters employed may be constitutive,
tissue-specific, or inducible and in certain embodiments may direct
high level expression of the introduced DNA segment under specified
conditions, such as large-scale production of recombinant proteins
or peptides.
[0130] Examples of inducible elements, which are regions of a
nucleic acid sequence that can be activated in response to a
specific stimulus, include but are not limited to Immunoglobulin
Heavy Chain (Banerji et al, 1983; Gilles et al, 1983; Grosschedl et
al, 1985; Atchinson et al, 1986, 1987; toiler et al, 1987;
Weinberger et al, 1984; Kiledjian et al, 1988; Porton et al; 1990),
Immunoglobulin Light Chain (Queen et al, 1983; Picard et al, 1984),
T Cell Receptor (Luria et al, 1987; Winoto et al, 1989; Redondo et
al; 1990), HLA DQ.alpha. and/or DQ.beta. (Sullivan et al, 1987),
.beta.-Interferon (Goodbourn et al, 1986; Fujita et al, 1987;
Goodbourn et al, 1988), Interleukin-2 (Greene et al, 1989),
Interleukin-2 Receptor (Greene et al, 1989; Lin et al, 1990), MHC
Class II 5 (Koch et al, 1989), MHC Class II HLA-DR.alpha. (Sherman
et al, 1989), .beta.-Actin (Kawamoto et al, 1988; Ng et al; 1989),
Muscle Creatine Kinase (MCK) (Jaynes et al, 1988; Horlick et al,
1989; Johnson et al, 1989), Prealbumin (Transthyretin) (Costa et
al, 1988), Elastase I (Omitz et al, 1987), Metallothionein (MTII)
(Karin et al, 1987; Culotta et al, 1989), Collagenase (Pinkert et
al, 1987; Angel et al, 1987), Albumin (Pinkert et al, 1987; Tranche
et al, 1989, 1990), .alpha.-Fetoprotein (Godbout et al, 1988;
Campere et al, 1989), .gamma.-Globin (Bodine et al, 1987;
Perez-Stable et al, 1990) .beta.-Globin (Trudel et al, 1987), c-fos
(Cohen et al, 1987), c-HA-ras (Triesman, 1986; Deschamps et al,
1985), Insulin (Edlund et al, 1985), Neural Cell Adhesion Molecule
(NCAM) (Hirsh et al, 1990), .alpha.l-Antitrypain (Larimer et al,
1990), H2B (TH2B) Histone (Hwang et al, 1990), Mouse and/or Type I
Collagen (Ripe et al, 1989), Glucose-Regulated Proteins (GRP94 and
GRP78) (Chang et al, 1989), Rat Growth Hormone (Larsen et al,
1986), Human Serum Amyloid A (SAA) (Edbrooke et al, 1989), Troponin
I (TN I) (Yutzey et al, 1989), Platelet-Derived Growth Factor
(PDGF) (Pech et al, 1989), Duchenne Muscular Dystrophy (Klamut et
al, 1990), SV40 (Banerji et al, 1981; Moreau et al, 1981; Sleigh et
al, 1985; Firak et al, 1986; Herr et al, 1986; Imbra et al, 1986;
Kadesch et al, 1986; Wang et al, 1986; Ondek et al, 1987; Kuhl et
al, 1987; Schaffner et al, 1988), Polyoma (Swartzendruber et al,
1975; Vasseur et al, 1980; Katinka et al, 1980, 1981; Tyndell et
al, 1981; Dandolo et al, 1983; de Villiers et al, 1984; Hen et al,
1986; Satake et al, 1988; Campbell et al, 1988), Retroviruses
(Kriegler et al, 1982, 1983; Levinson et al, 1982; Kriegler et al,
1983, 1984a, b, 1988; Bosze et al, 1986; Miksicek et al, 1986;
Celander et al, 1987; Thiesen et al, 1988; Celander et al, 1988;
Choi et al, 1988; Reisman et al, 1989), Papilloma Virus (Campo et
al, 1983; Lusky et al, 1983; Spandidos and Wilkie, 1983; Spalholz
et al, 1985; Lusky et al, 1986; Cripe et al, 1987; Gloss et al,
1987; Hirochika et al, 1987; Stephens et al, 1987), Hepatitis B
Virus (Bulla et al, 1986; Jameel et al, 1986; Shaul et al, 1987;
Spandau et al, 1988; Vannice et al, 1988), Human Immunodeficiency
Virus (Muesing et al, 1987; Hauber et al, 1988; Jakobovits et al,
1988; Feng et al, 1988; Takebe et al, 1988; Rosen et al, 1988;
Berkhout et al, 1989; Laspia et al, 1989; Sharp et al, 1989;
Braddock et al, 1989), Cytomegalovirus (CMV) IE (Weber et al, 1984;
Boshart et al, 1985; Foecking et al, 1986), Gibbon Ape Leukemia
Virus (Holbrook et al, 1987; Quinn et al, 1989).
[0131] Inducible Elements include, but are not limited to MT
II--Phorbol Ester (TFA)/Heavy metals (Palmiter et al, 1982;
Haslinger et al, 1985; Searle et al, 1985; Stuart et al, 1985;
Imagawa et al, 1987, Karin et al, 1987; Angel et al, 1987b; McNeall
et al, 1989); MMTV (mouse mammary tumor virus)--Glucocorticoids
(Huang et al, 1981; Lee et al, 1981; Majors et al, 1983; Chandler
et al, 1983; Lee et al, 1984; Ponta et al, 1985; Sakai et al,
1988); .beta.-Interferon--poly(rl)x/poly(rc) (Tavernier et al,
1983); Adenovirus 5 E2--EIA (Imperiale et al, 1984);
Collagenase--Phorbol Ester (TPA) (Angel et al, 1987a);
Stromelysin--Phorbol Ester (TPA) (Angel et al, 1987b);
SV40--Phorbol Ester (TPA) (Angel et al, 1987b); Murine MX
Gene--Interferon, Newcastle Disease Virus (Hug et al, 1988); GRP78
Gene--A23187 (Resendez et al, 1988); .alpha.-2-Macroglobulin--IL-6
(Kunz et al, 1989); Vimentin--Serum (Rittling et al, 1989); MHC
Class I Gene H-2Kb--Interferon (Blanar et al, 1989);
HSP70--E1A/SV40 Large T Antigen (Taylor et al, 1989, 1990a, 1990b);
Proliferin--Phorbol Ester/TPA (Mordacq et al, 1989); Tumor Necrosis
Factor--PMA (Hensel et al, 1989); and Thyroid Stimulating Hormonea
Gene--Thyroid Hormone (Chatterjee et al, 1989).
[0132] Also contemplated as useful in the present invention are the
dectin-1 and dectin-2 promoters. Additionally any promoter/enhancer
combination (as per the Eukaryotic Promoter Data Base EPDB) could
also be used to drive expression of structural genes encoding
oligosaccharide processing enzymes, protein folding accessory
proteins, selectable marker proteins or a heterologous protein of
interest.
[0133] The particular promoter that is employed to control the
expression of peptide or protein encoding polynucleotide of the
invention is not believed to be critical, so long as it is capable
of expressing the polynucleotide in a targeted cell, preferably a
bacterial cell. Where a human cell is targeted, it is preferable to
position the polynucleotide coding region adjacent to and under the
control of a promoter that is capable of being expressed in a human
cell. Generally speaking, such a promoter might include either a
bacterial, human or viral promoter.
[0134] In various embodiments, the human cytomegalovirus (CMV)
immediate early gene promoter, the SV40 early promoter, and the
Rous sarcoma virus long terminal repeat can be used to obtain high
level expression of a related polynucleotide to this invention. The
use of other viral or mammalian cellular or bacterial phage
promoters, which are well known in the art, to achieve expression
of polynucleotides is contemplated as well.
[0135] In embodiments in which a vector is administered to a
subject for expression of the protein, it is contemplated that a
desirable promoter for use with the vector is one that is not
down-regulated by cytokines or one that is strong enough that even
if down-regulated, it produces an effective amount of the
protein/polypeptide of the current invention in a subject to elicit
an immune response. Non-limiting examples of these are CMV IE and
RSV LTR. In other embodiments, a promoter that is up-regulated in
the presence of cytokines is employed. The MHC I promoter increases
expression in the presence of IFN-.gamma..
[0136] Tissue specific promoters can be used, particularly if
expression is in cells in which expression of an antigen is
desirable, such as dendritic cells or macrophages. The mammalian
MHC I and MHC II promoters are examples of such tissue-specific
promoters. 2. Initiation Signals and Internal Ribosome Binding
Sites (IRES)
[0137] A specific initiation signal also may be required for
efficient translation of coding sequences. These signals include
the ATG initiation codon or adjacent sequences. Exogenous
translational control signals, including the ATG initiation codon,
may need to be provided. One of ordinary skill in the art would
readily be capable of determining this and providing the necessary
signals. It is well known that the initiation codon must be
"in-frame" with the reading frame of the desired coding sequence to
ensure translation of the entire insert. The exogenous
translational control signals and initiation codons can be either
natural or synthetic and may be operable in bacteria or mammalian
cells. The efficiency of expression may be enhanced by the
inclusion of appropriate transcription enhancer elements.
[0138] In certain embodiments of the invention, the use of internal
ribosome entry sites (IRES) elements are used to create multigene,
or polycistronic, messages. IRES elements are able to bypass the
ribosome scanning model of 5' methylated Cap dependent translation
and begin translation at internal sites (Pelletier and Sonenberg,
1988). IRES elements from two members of the picornavirus family
(polio and encephalomyocarditis) have been described (Pelletier and
Sonenberg, 1988), as well an IRES from a mammalian message (Macejak
and Sarnow, 1991). IRES elements can be linked to heterologous open
reading frames. Multiple open reading frames can be transcribed
together, each separated by an IRES, creating polycistronic
messages. By virtue of the IRES element, each open reading frame is
accessible to ribosomes for efficient translation. Multiple genes
can be efficiently expressed using a single promoter/enhancer to
transcribe a single message (see U.S. Pat. Nos. 5,925,565 and
5,935,819, herein incorporated by reference).
2. Multiple Cloning Sites
[0139] Vectors can include a multiple cloning site (MCS), which is
a nucleic acid region that contains multiple restriction enzyme
sites, any of which can be used in conjunction with standard
recombinant technology to digest the vector. (See Carbonelli et al,
1999, Levenson et al, 1998, and Cocea, 1997, incorporated herein by
reference.) Frequently, a vector is linearized or fragmented using
a restriction enzyme that cuts within the MCS to enable exogenous
sequences to be ligated to the vector. Techniques involving
restriction enzymes and ligation reactions are well known to those
of skill in the art of recombinant technology.
3. Splicing Sites
[0140] Most transcribed eukaryotic RNA molecules will undergo RNA
splicing to remove introns from the primary transcripts. If
relevant in the context of vectors of the present invention,
vectors containing genomic eukaryotic sequences may require donor
and/or acceptor splicing sites to ensure proper processing of the
transcript for protein expression. (See Chandler et al, 1997,
incorporated herein by reference.)
4. Termination Signals
[0141] The vectors or constructs of the present invention will
generally comprise at least one termination signal. A "termination
signal" or "terminator" is comprised of the DNA sequences involved
in specific termination of an RNA transcript by an RNA polymerase.
Thus, in certain embodiments a termination signal that ends the
production of an RNA transcript is contemplated. A terminator may
be necessary in vivo to achieve desirable message levels.
[0142] In eukaryotic systems, the terminator region may also
comprise specific DNA sequences that permit site-specific cleavage
of the new transcript so as to expose a polyadenylation site. This
signals a specialized endogenous polymerase to add a stretch of
about 200 A residues (poly A) to the 3' end of the transcript. RNA
molecules modified with this polyA tail appear to more stable and
are translated more efficiently. Thus, in other embodiments
involving eukaryotes, it is preferred that that terminator
comprises a signal for the cleavage of the RNA, and it is more
preferred that the terminator signal promotes polyadenylation of
the message.
[0143] Terminators contemplated for use in the invention include
any known terminator of transcription described herein or known to
one of ordinary skill in the art, including but not limited to, for
example, the bovine growth hormone terminator or viral termination
sequences, such as the SV40 terminator. In certain embodiments, the
termination signal may be a lack of transcribable or translatable
sequence, such as due to a sequence truncation.
5. Polyadenylation Signals
[0144] In expression, particularly eukaryotic expression (as is
relevant in nucleic acid vaccination), one will typically include a
polyadenylation signal to effect proper polyadenylation of the
transcript. The nature of the polyadenylation signal is not
believed to be crucial to the successful practice of the invention,
and/or any such sequence may be employed. Preferred embodiments
include the SV40 polyadenylation signal and/or the bovine growth
hormone polyadenylation signal, convenient and/or known to function
well in various target cells. Polyadenylation may increase the
stability of the transcript or may facilitate cytoplasmic
transport.
6. Origins of Replication
[0145] In order to propagate a vector in a host cell, it may
contain one or more origins of replication sites (often termed
"on"), which is a specific nucleic acid sequence at which
replication is initiated. Alternatively an autonomously replicating
sequence (ARS) can be employed if the host cell is yeast.
7. Selectable and Screenable Markers
[0146] In certain embodiments of the invention, cells containing a
nucleic acid construct of the present invention may be identified
in vitro or in vivo by encoding a screenable or selectable marker
in the expression vector. When transcribed and translated, a marker
confers an identifiable change to the cell permitting easy
identification of cells containing the expression vector.
Generally, a selectable marker is one that confers a property that
allows for selection. A positive selectable marker is one in which
the presence of the marker allows for its selection, while a
negative selectable marker is one in which its presence prevents
its selection. An example of a positive selectable marker is a drug
resistance marker.
[0147] Usually the inclusion of a drug selection marker aids in the
cloning and identification of transformants, for example, markers
that confer resistance to neomycin, puromycin, hygromycin, DHFR,
GPT, zeocin or histidinol are useful selectable markers. In
addition to markers conferring a phenotype that allows for the
discrimination of transformants based on the implementation of
conditions, other types of markers including screenable markers
such as GFP for colorimetric analysis. Alternatively, screenable
enzymes such as herpes simplex virus thymidine kinase (tk) or
chloramphenicol acetyltransferase (CAT) may be utilized. One of
skill in the art would also know how to employ immunologic markers
that can be used in conjunction with FACS analysis. The marker used
is not believed to be important, so long as it is capable of being
expressed simultaneously with the nucleic acid encoding a protein
of the invention. Further examples of selectable and screenable
markers are well known to one of skill in the art.
The Transformed Cells of the Invention
[0148] Transformed cells of the invention are useful as organisms
for producing the polypeptide of the invention, but also as simple
"containers" of nucleic acids and vectors of the invention.
[0149] Certain transformed cells of the invention are capable of
replicating the nucleic acid fragment defined for option i) of the
second aspect of the invention. Preferred transformed cells of the
invention are capable of expressing the nucleic acid fragment
defined for option i).
[0150] For recombinant production it is convenient, but not a
prerequisite that the transformed cell according is prokaryotic,
such as a bacterium, but generally both prokaryotic cells and
eukaryotic cells may be used.
[0151] Suitable prokaryotic cells are bacterial cells selected from
the group consisting of Escherichia (such as E. coli.), Bacillus
[e.g. Bacillus subtilis], Salmonella, and Mycobacterium [preferably
non-pathogenic, e.g. M. bovis BCG].
[0152] Eukaryotic cells can be in the form of yeasts (such as
Saccharomyces cerevisiae) and protozoans. Alternatively, the
transformed eukaryotic cells are derived from a multicellular
organism such as a fungus, an insect cell, a plant cell, or a
mammalian cell.
[0153] For production purposes, it is advantageous that the
transformed cell of the invention is stably transformed by having
the nucleic acid defined above for option i) stably integrated into
its genome, and in certain embodiments it is also preferred that
the transformed cell secretes or carries on its surface the
polypeptide of the invention, since this facilitates recovery of
the polypeptides produced. A particular version of this embodiment
is one where the transformed cell is a bacterium and secretion of
the polypeptide of the invention is into the periplasmic space.
[0154] As noted above, stably transformed cells are
preferred--these i.a. allows that cell lines comprised of
transformed cells as defined herein may be established--such cell
lines are particularly preferred aspects of the invention.
[0155] Further details on cells and cell lines are presented in the
following:
[0156] Suitable cells for recombinant nucleic acid expression of
the nucleic acid fragments of the present invention are prokaryotes
and eukaryotes. Examples of prokaryotic cells include E. coli;
members of the Staphylococcus genus, such as S. epidermidis;
members of the Lactobacillus genus, such as L. plantarum; members
of the Lactococcus genus, such as L. lactis; members of the
Bacillus genus, such as B. subtilis; members of the Corynebacterium
genus such as C. glutamicum; and members of the Pseudomonas genus
such as Ps. fluorescens. Examples of eukaryotic cells include
mammalian cells; insect cells; yeast cells such as members of the
Saccharomyces genus (e.g. S. cerevisiae), members of the Pichia
genus (e.g. P. pastoris), members of the Hansenula genus (e.g. H.
polymorpha), members of the Kluyveromyces genus (e.g. K. lactis or
K. fragilis) and members of the Schizosaccharomyces genus (e.g. S.
pombe).
[0157] Techniques for recombinant gene production, introduction
into a cell, and recombinant gene expression are well known in the
art. Examples of such techniques are provided in references such as
Ausubel, Current Protocols in Molecular Biology, John Wiley,
1987-2002, and Sambrook et al., Molecular Cloning, A Laboratory
Manual, 2 nd Edition, Cold Spring Harbor Laboratory Press,
1989.
[0158] As used herein, the terms "cell," "cell line," and "cell
culture" may be used interchangeably. All of these terms also
include their progeny, which is any and all subsequent generations.
It is understood that all progeny may not be identical due to
deliberate or inadvertent mutations. In the context of expressing a
heterologous nucleic acid sequence, "host cell" refers to a
prokaryotic or eukaryotic cell, and it includes any transformable
organism that is capable of replicating a vector or expressing a
heterologous gene encoded by a vector. A host cell can, and has
been, used as a recipient for vectors or viruses. A host cell may
be "transfected" or "transformed," which refers to a process by
which exogenous nucleic acid, such as a recombinant
protein-encoding sequence, is transferred or introduced into the
host cell. A transformed cell includes the primary subject cell and
its progeny.
[0159] Host cells may be derived from prokaryotes or eukaryotes,
including bacteria, yeast cells, insect cells, and mammalian cells
for replication of the vector or expression of part or all of the
nucleic acid sequence(s). Numerous cell lines and cultures are
available for use as a host cell, and they can be obtained through
the American Type Culture Collection (ATCC), which is an
organization that serves as an archive for living cultures and
genetic materials (www.atcc.org) or from other depository
institutions such as Deutsche Sammlung vor Micrroorganismen and
Zellkulturen (DSM). An appropriate host can be determined by one of
skill in the art based on the vector backbone and the desired
result. A plasmid or cosmid, for example, can be introduced into a
prokaryote host cell for replication of many vectors or expression
of encoded proteins. Bacterial cells used as host cells for vector
replication and/or expression include Staphylococcus strains, DH5a,
JMI 09, and KC8, as well as a number of commercially available
bacterial hosts such as SURE.RTM. Competent Cells and SOLOP ACK.TM.
Gold Cells (STRATAGENE.RTM., La Jolla, Calif.). Alternatively,
bacterial cells such as E. coli LE392 could be used as host cells
for phage viruses. Appropriate yeast cells include Saccharomyces
cerevisiae, Saccharomyces pombe, and Pichia pastoris.
[0160] Examples of eukaryotic host cells for replication and/or
expression of a vector include HeLa, NIH3T3, Jurkat, 293, Cos, CHO,
Saos, and PC12. Many host cells from various cell types and
organisms are available and would be known to one of skill in the
art. Similarly, a viral vector may be used in conjunction with
either a eukaryotic or prokaryotic host cell, particularly one that
is permissive for replication or expression of the vector.
[0161] Some vectors may employ control sequences that allow it to
be replicated and/or expressed in both prokaryotic and eukaryotic
cells. One of skill in the art would further understand the
conditions under which to incubate all of the above described host
cells to maintain them and to permit replication of a vector. Also
understood and known are techniques and conditions that would allow
large-scale production of vectors, as well as production of the
nucleic acids encoded by vectors and their cognate polypeptides,
proteins, or peptides.
Expression Systems
[0162] Numerous expression systems exist that comprise at least a
part or all of the compositions discussed above. Prokaryote- and/or
eukaryote-based systems can be employed for use with the present
invention to produce nucleic acid sequences, or their cognate
polypeptides, proteins and peptides. Many such systems are
commercially and widely available.
[0163] The insect cell/baculovirus system can produce a high level
of protein expression of a heterologous nucleic acid segment, such
as described in U.S. Pat. Nos. 5,871,986, 4,879,236, both herein
incorporated by reference, and which can be bought, for example,
under the name MAXBAC.RTM. 2.0 from INVITROGEN.RTM. and BACPACK.TM.
Baculovirus expression system from CLONTECH.RTM.
[0164] In addition to the disclosed expression systems of the
invention, other examples of expression systems include
STRATAGENE.RTM.'s COMPLETE CONTROL''' Inducible Mammalian
Expression System, which involves a synthetic ecdysone-inducible
receptor, or its pET Expression System, an E. coli expression
system. Another example of an inducible expression system is
available from INVITROGEN.RTM., which carries the T-REX.TM.
(tetracycline-regulated expression) System, an inducible mammalian
expression system that uses the full-length CMV promoter.
INVITROGEN.RTM. also provides a yeast expression system called the
Pichia methanolica Expression System, which is designed for
high-level production of recombinant proteins in the methylotrophic
yeast Pichia methanolica. One of skill in the art would know how to
express a vector, such as an expression construct, to produce a
nucleic acid sequence or its cognate polypeptide, protein, or
peptide.
Amplification of Nucleic Acids
[0165] Nucleic acids used as a template for amplification may be
isolated from cells, tissues or other samples according to standard
methodologies (Sambrook et al, 2001). In certain embodiments,
analysis is performed on whole cell or tissue homogenates or
biological fluid samples without substantial purification of the
template nucleic acid. The nucleic acid may be genomic DNA or
fractionated or whole cell RNA. Where RNA is used, it may be
desired to first convert the RNA to a complementary DNA.
[0166] The term "primer," as used herein, is meant to encompass any
nucleic acid that is capable of priming the synthesis of a nascent
nucleic acid in a template-dependent process. Typically, primers
are oligonucleotides from ten to twenty and/or thirty base pairs in
length, but longer sequences can be employed. Primers may be
provided in double-stranded and/or single-stranded form, although
the single-stranded form is preferred.
[0167] Pairs of primers designed to selectively hybridize to
nucleic acids corresponding to sequences of genes identified herein
are contacted with the template nucleic acid under conditions that
permit selective hybridization. Depending upon the desired
application, high stringency hybridization conditions may be
selected that will only allow hybridization to sequences that are
completely complementary to the primers. In other embodiments,
hybridization may occur under reduced stringency to allow for
amplification of nucleic acids containing one or more mismatches
with the primer sequences. Once hybridized, the template-primer
complex is contacted with one or more enzymes that facilitate
template-dependent nucleic acid synthesis. Multiple rounds of
amplification, also referred to as "cycles," are conducted until a
sufficient amount of amplification product is produced.
[0168] The amplification product may be detected or quantified. In
certain applications, the detection may be performed by visual
means. Alternatively, the detection may involve indirect
identification of the product via chemiluminescence, radioactive
scintigraphy of incorporated radiolabel or fluorescent label or
even via a system using electrical and/or thermal impulse signals
(Bellus, 1994).
[0169] A number of template dependent processes are available to
amplify the oligonucleotide sequences present in a given template
sample. One of the best known amplification methods is the
polymerase chain reaction (referred to as PCR.TM.) which is
described in detail in U.S. Pat. Nos. 4,683,195, 4,683,202 and
4,800,159, and in Innis et al., 1988, each of which is incorporated
herein by reference in their entirety.
[0170] Alternative methods for amplification of target nucleic acid
sequences that may be used in the practice of the present invention
are disclosed in U.S. Pat. Nos. 5,843,650, 5,846,709, 5,846,783,
5,849,546, 5,849,497, 5,849,547, 5,858,652, 5,866,366, 5,916,776,
5,922,574, 5,928,905, 5,928,906, 5,932,451, 5,935,825, 5,939,291
and 5,942,391, GB Application No. 2 202 328, and in PCT Application
No. PCT/US89/01025, each of which is incorporated herein by
reference in its entirety.
Methods of Gene Transfer
[0171] Suitable methods for nucleic acid delivery to effect
expression of compositions of the present invention are believed to
include virtually any method by which a nucleic acid (e.g., DNA,
including viral and nonviral vectors) can be introduced into a
cell, a tissue or an organism, as described herein or as would be
known to one of ordinary skill in the art. Such methods include,
but are not limited to, direct delivery of DNA such as by injection
(U.S. Pat. Nos. 5,994,624, 5,981,274, 5,945,100, 5,780,448,
5,736,524, 5,702,932, 5,656,610, 5,589,466 and 5,580,859, each
incorporated herein by reference), including microinjection
(Harland and Weintraub, 1985; U.S. Pat. No. 5,789,215, incorporated
herein by reference); by electroporation (U.S. Pat. No. 5,384,253,
incorporated herein by reference); by calcium phosphate
precipitation (Graham and Van Der Eb, 1973; Chen and Okayama, 1987;
Rippe et al., 1990); by using DEAE dextran followed by polyethylene
glycol (Gopal, 1985); by direct sonic loading (Fechheimer et al,
1987); by liposome mediated transfection (Nicolau and Sene, 1982;
Fraley et al, 1979; Nicolau et al, 1987; Wong et al, 1980; Kaneda
et al, 1989; Kato et al, 1991); by microprojectile bombardment (PCT
Application Nos. WO 94/09699 and 95/06128; U.S. Pat. Nos.
5,610,042; 5,322,783 5,563,055, 5,550,318, 5,538,877 and 5,538,880,
and each incorporated herein by reference); by agitation with
silicon carbide fibers (Kaeppler et al, 1990; U.S. Pat. Nos.
5,302,523 and 5,464,765, each incorporated herein by reference); by
Agrobacterium mediated transformation (U.S. Pat. Nos. 5,591,616 and
5,563,055, each incorporated herein by reference); or by PEG
mediated transformation of protoplasts (Omirulleh et al, 1993; U.S.
Pat. Nos. 4,684,611 and 4,952,500, each incorporated herein by
reference); by desiccation/inhibition mediated DNA uptake (Potrykus
et al, 1985). Through the application of techniques such as these,
organelle(s), cell(s), tissue(s) or organism(s) may be stably or
transiently transformed.
The Antibodies of the Invention--and their Production/Isolation
[0172] Antibodies directed against the proteins of the invention
are useful for affinity chromatography, immunoassays, and for
distinguishing/identifying staphylococcus proteins as well as for
passive immunisation and therapy.
[0173] Antibodies to the proteins of the invention, both polyclonal
and monoclonal, may be prepared by conventional methods. In
general, the protein is first used to immunize a suitable animal,
preferably a mouse, rat, rabbit or goat. Rabbits and goats are
preferred for the preparation of polyclonal sera due to the volume
of serum obtainable, and the availability of labeled anti-rabbit
and anti-goat antibodies. Immunization is generally performed by
mixing or emulsifying the protein in saline, preferably in an
adjuvant such as Freund's complete adjuvant, and injecting the
mixture or emulsion parenterally (generally subcutaneously or
intramuscularly). A dose of 50-200 .mu.g/injection is typically
sufficient. Immunization is generally boosted 2-6 weeks later with
one or more injections of the protein in saline, preferably using
Freund's incomplete adjuvant. One may alternatively generate
antibodies by in vitro immunization using methods known in the art,
which for the purposes of this invention is considered equivalent
to in vivo immunization. Polyclonal antiserum is obtained by
bleeding the immunized animal into a glass or plastic container,
incubating the blood at 25 C for one hour, followed by incubating
at 4 C for 2-18 hours. The serum is recovered by centrifugation
(eg. 1,000 g for 10 minutes). About 20-50 ml per bleed may be
obtained from rabbits.
[0174] Monoclonal antibodies are prepared using the standard method
of Kohler & Milstein [Nature (1975) 256: 495-96], or a
modification thereof. Typically, a mouse or rat is immunized as
described above. However, rather than bleeding the animal to
extract serum, the spleen (and optionally several large lymph
nodes) is removed and dissociated into single cells. If desired,
the spleen cells may be screened (after removal of nonspecifically
adherent cells) by applying a cell suspension to a plate or well
coated with the protein antigen. B-cells expressing membrane-bound
immunoglobulin specific for the antigen bind to the plate, and are
not rinsed away with the rest of the suspension. Resulting B-cells,
or all dissociated spleen cells, are then induced to fuse with
myeloma cells to form hybridomas, and are cultured in a selective I
aedium (elg. hypexanthine, aminopterin, thymidine medium, "HAT").
The resulting hybridomas are plated by limiting dilution, and are
assayed for production of antibodies, which bind specifically to
the immunizing antigen (and which do not bind to unrelated
antigens). The selected MAb-secreting hybridomas are then cultured
either in vitro (eg. in tissue culture bottles or hollow fiber
reactors), or in vivo (as ascites in mice).
[0175] If desired, the antibodies (whether polyclonal or
monoclonal) may be labeled using conventional techniques. Suitable
labels include fluorophores, chromophores, radioactive atoms
(particularly 32p and 125I), electron-dense reagents, enzymes, and
ligands having specific binding partners. Enzymes are typically
detected by their activity. For example, horseradish peroxidase is
usually detected by its ability to convert 3,3',
5,5'-tetramethylbenzidine (TMB) to a blue pigment, quantifiable
with a spectrophotometer. "Specific binding partner" refers to a
protein capable of binding a ligand molecule with high specificity,
as for example in the case of an antigen and a monoclonal antibody
specific therefor. Other specific binding partners include biotin
and avidin or streptavidin, IgG and protein A, and the numerous
receptor-ligand couples known in the art. It should be understood
that the above description is not meant to categorize the various
labels into distinct classes, as the same label may serve in
several different modes. For example, 1151 may serve as a
radioactive label or as an electron-dense reagent. HRP may serve as
enzyme or as antigen for a MAb. Further, one may combine various
labels for desired effect. For example, MAbs and avidin also
require labels in the practice of this invention: thus, one might
label a MAb with biotin, and detect its presence with avidin
labeled with, 125I, or with an anti-biotin MAb labeled with HRP.
Other permutations and possibilities will be readily apparent to
those of ordinary skill in the art, and are considered as
equivalents within the scope of the instant invention.
[0176] According to the invention, the isolated monoclonal antibody
or antibody analogue is preferably a monoclonal antibody selected
from a multi-domain antibody such as a murine antibody, a chimeric
antibody such as a humanized antibody, a fully human antibody, and
single-domain antibody of a llama or a camel, or which is an
antibody analogue selected from a fragment of an antibody such as
an Fab or an F(ab').sub.2, an scFV; cf. also the definition of the
term "antibody" presented above.
Compositions of the Invention; Vaccines
[0177] Pharmaceutical compositions, in particular vaccines,
according to the invention may either be prophylactic (ie. to
prevent infection) or therapeutic (ie, to treat disease after
infection).
[0178] Such vaccines comprise immunising antigen(s), immunogen(s),
polypeptide(s), protein(s) or nucleic acid(s), usually in
combination with "pharmaceutically acceptable carriers", which
include any carrier that does not itself induce the production of
antibodies harmful to the individual receiving the composition.
Suitable carriers are typically large, slowly metabolized
macromolecules such as proteins, polysaccharides, polylactic acids,
polyglycolic acids, polymeric amino acids, amino acid copolymers,
lipid aggregates (such as oil droplets or liposomes), and inactive
virus particles.
[0179] Such carriers are well known to those of ordinary skill in
the art. Additionally, these carriers may function as
immunostimulating agents ("adjuvants"). Furthermore, the antigen or
immunogen may be conjugated to a bacterial toxoid, such as a toxoid
from diphtheria, tetanus, cholera, H. pylori, etc. pathogen, cf.
the description of immunogenic carriers supra.
[0180] The pharmaceutical compositions of the invention thus
typically contain an immunological adjuvant, which is commonly an
aluminium based adjuvant or one of the other adjuvants described in
the following:
[0181] Preferred adjuvants to enhance effectiveness of the
composition include, but are not limited to: (1) aluminum salts
(alum), such as aluminum hydroxide, aluminum phosphate, aluminum
sulfate, etc; (2) oil-in-water emulsion formulations (with or
without other specific immunostimulating agents such as muramyl
peptides (see below) or bacterial cell wall components), such as
for example (a) MF59 (WO 90/14837; Chapter 10 in Vaccine design:
the subunit and adjuvant approach, eds. Powell & Newman, Plenum
Press 1995), containing 5% Squalene, 0.5% Tween 80, and 0.5% Span
85 (optionally containing various amounts of MTP-PE (see below),
although not required) formulated into submicron particles using a
microfluidizer such as Model 110Y microfluidizer (Microfluidics,
Newton, Mass.), (b) SAF, containing 10% Squalane, 0.4% Tween 80, 5%
pluronic-blocked polymer L121, and thr-MDP (see below) either
microfluidized into a submicron emulsion or vortexed to generate a
larger particle size emulsion, and (c) Ribi adjuvant system (RAS),
(Ribi Immunochem, Hamilton, Mont.) containing 2% Squalene, 0.2%
Tween 80, and one or more bacterial cell wall components from the
group consisting of monophosphoryl lipid A (MPL), trehalose
dimycolate (TDM), and cell wall skeleton (CWS), preferably MPL+CWS
(Detox.TM.); (3) saponin adjuvants such as Stimulon.TM. (Cambridge
Bioscience, Worcester, Mass.) may be used or particles generated
therefrom such as ISCOMs (immunostimulating complexes); (4)
Complete Freund's Adjuvant (CFA) and Incomplete Freund's Adjuvant
(IFA); (5) cytokines, such as interleukins (eg. IL-1, IL-2, IL-4,
IL-5, IL-6, IL-7, IL-12, etc.), interferons (eg. gamma interferon),
macrophage colony stimulating factor (M-CSF), tumor necrosis factor
(TNF), etc.; and (6) other substances that act as immunostimulating
agents to enhance the effectiveness of the composition. Alum and
MF59.TM. adjuvants are preferred.
[0182] As mentioned above, muramyl peptides include, but are not
limited to, N-acetyl-muramyl-L-threonyl-D-isoglutamine (thr-MDP),
N-acetyl-normuramyl-L-alanyl-D-isoglutamine (nor-MDP),
N-acetylmuramyl-L-alanyl-D-isoglutaminyl-L-alanine-2''-2'-dipalmitoyl-sn--
glycero-3-hydroxyphosphoryloxy)-ethylamine (MTP-PE), etc.
[0183] The immunogenic compositions (eg. the immunising antigen or
immunogen or polypeptide or protein or nucleic acid,
pharmaceutically acceptable carrier, and adjuvant) typically will
contain diluents, such as water, saline, glycerol, ethanol, etc.
Additionally, auxiliary substances, such as wetting or emulsifying
agents, pH buffering substances, and the like, may be present in
such vehicles.
[0184] Typically, the immunogenic compositions are prepared as
injectables, either as liquid solutions or suspensions; solid forms
suitable for solution in, or suspension in, liquid vehicles prior
to injection may also be prepared. The preparation also may be
emulsified or encapsulated in liposomes for enhanced adjuvant
effect, as discussed above under pharmaceutically acceptable
carriers.
[0185] Immunogenic compositions used as vaccines comprise an
immunologically effective amount of the antigenic or immunogenic
polypeptides, as well as any other of the above-mentioned
components, as needed. By "immunollogically effective amount", it
is meant that the administration of that amount to an individual,
either in a single dose or as part of a series, is effective for
treatment or prevention. This amount varies depending upon the
health and physical condition of the individual to be treated, the
taxonomic group of individual to be treated (eg. nonhuma primate,
primate, etc.), the capacity of the individual's immune system to
synthesize antibodies or generally mount an immune response, the
degree of protection desired, the formulation of the vaccine, the
treating doctor's assessment of the medical situation, and other
relevant factors. It is expected that the amount will fall in a
relatively broad range that can be determined through routine
trials. However, for the purposes of protein vaccination, the
amount administered per immunization is typically in the range
between 0.5 .mu.g and 500 mg (however, often not higher than 5,000
.mu.g), and very often in the range between 10 and 200 .mu.g.
[0186] The immunogenic compositions are conventionally administered
parenterally, eg, by injection, either subcutaneously,
intramuscularly, or transdermally/transcutaneously (eg. WO
98/20734). Additional formulations suitable for other modes of
administration include oral and pulmonary formulations,
suppositories, and transdermal applications. In the case of nucleic
acid vaccination, also the intravenous or intraarterial routes may
be applicable.
[0187] Dosage treatment may be a single dose schedule or a multiple
dose schedule. The vaccine may be administered in conjunction with
other immunoregulatory agents.
[0188] As an alternative to protein-based vaccines, DNA vaccination
(also termed nucleic acid vaccination or gene vaccination) may be
used [eg. Robinson & Torres (1997) Seminars in Imlllunol 9:
271-283; Donnelly et al. (1997) Avnu Rev Innnunol 15: 617-648;
later herein].
[0189] A further aspect of the invention is the recognition that
combination vaccines can be provided, wherein 2 or more antigens
disclosed herein are combined to enhance the immune response by the
vaccinated animal, including to optimize initial immune response
and duration of immunity. For the purposes of this aspect of the
invention, multiple antigenic fragments derived from the same,
longer protein can also be used, such as the use a combination of
different lengths of polypeptide sequence fragments from one
protein.
[0190] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 1 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0191] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 2 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0192] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 3 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0193] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 4 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0194] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 5 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0195] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 6 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0196] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 7 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0197] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 8 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0198] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 9 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0199] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 10 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0200] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 11 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0201] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 12 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0202] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 13 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0203] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 14 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0204] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 15 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0205] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 16 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0206] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 17 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0207] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 18 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0208] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 19 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0209] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 20 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0210] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 21 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0211] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 22 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0212] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 23 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0213] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 24 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0214] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 25 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0215] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 26 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0216] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 27 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0217] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 28 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0218] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 29 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
[0219] Thus, embodiments of the invention relate to a composition
(or the use as a vaccine of) comprising 2 distinct (i.e.
non-identical) proteinaceaous immunogens disclosed herein wherein
the first of said immunogens is SEQ ID NO: 30 or a variant or
fragment thereof disclosed herein in combination with a
proteinaceous immunogen selected from any one of SEQ ID NOs: 1, 2,
3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20,
21, 22, 23, 24, 25, 26, 27, 28, 29, and 30, or a variant or
fragment disclosed herein of any one of SEQ ID NOs: 1, 2, 3, 4, 5,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23,
24, 25, 26, 27, 28, 29, and 30.
Treatment Methods of the Invention
[0220] The method of the sixth aspect of the invention generally
relates to induction of immunity and as such also entails method
that relate to treatment, prophylaxis and amelioration of
disease.
[0221] When immunization methods entail that a polypeptide of the
invention or a composition comprising such a polypeptide is
administered the animal (e.g. the human) typically receives between
0.5 and 5,000 .mu.g of the polypeptide of the invention per
administration.
[0222] In preferred embodiments of the sixth aspect, the
immunization scheme includes that the animal (e.g. the human)
receives a priming administration and one or more booster
administrations.
[0223] Preferred embodiments of the 6.sup.th aspect of the
invention comprise that the administration is for the purpose of
inducing protective immunity against A. baumannii. In this
embodiment it is particularly preferred that the protective
immunity is effective in reducing the risk of attracting infection
with A. baumannii or is effective in treating or ameliorating
infection with A. baumannii.
[0224] As mentioned herein, the preferred vaccines of the invention
induce humoral immunity, so it is preferred that the administration
is for the purpose of inducing antibodies specific for A. baumannii
and wherein said antibodies or B-lymphocytes producing said
antibodies are subsequently recovered from the animal.
[0225] But, as also mentioned the method of the 6.sup.th aspect may
also be useful in antibody production, so in other embodiments the
administration is for the purpose of inducing antibodies specific
for A. baumannii and wherein B-lymphocytes producing said
antibodies are subsequently recovered from the animal and used for
preparation of monoclonal antibodies.
[0226] Pharmaceutical compositions can as mentioned above comprise
polypeptides, antibodies, or nucleic acids of the invention. The
pharmaceutical compositions will comprise a therapeutically
effective amount thereof.
[0227] The term "therapeutically effective amount" or
"prophylactically effective amount" as used herein refers to an
amount of a therapeutic agent to treat, ameliorate, or prevent a
desired disease or condition, or to exhibit a detectable
therapeutic or preventative effect. The effect can be detected by,
for example, chemical markers or antigen levels. Therapeutic
effects also include reduction in physical symptoms, such as
decreased body temperature. The precise effective amount for a
subject will depend upon the subject's size and health, the nature
and extent of the condition, and the therapeutics or combination of
therapeutics selected for administration. Thus, it is not useful to
specify an exact effective amount in advance. Reference is however
made to the ranges for dosages of immunologically effective amounts
of polypeptides, cf. above.
[0228] However, the effective amount for a given situation can be
determined by routine experimentation and is within the judgement
of the clinician.
[0229] For purposes of the present invention, an effective dose
will be from about 0.01 mg/kg to 50 mg/kg or 0.05 mg/kg to about 10
mg/kg of the DNA or RNA constructs in the individual to which it is
administered.
[0230] A pharmaceutical composition can also contain a
pharmaceutically acceptable carrier. The term "pharmaceutically
acceptable carrier" refers to a carrier for administration of a
therapeutic agent, such as antibodies or a polypeptide, genes, and
other therapeutic agents. The term refers to any pharmaceutical
carrier that does not itself induce the production of antibodies
harmful to the individual receiving the composition, and which may
be administered without undue toxicity. Suitable carriers may be
large, slowly metabolized macromolecules such as proteins,
polysaccharides, polylactic acids, polyglycolic acids, polymeric
amino acids, amino acid copolymers, and inactive virus particles.
Such carriers are well known to those of ordinary skill in the
art.
[0231] Pharmaceutically acceptable salts can be used therein, for
example, mineral acid salts such as hydrochlorides, hydrobromides,
phosphates, sulfates, and the like; and the salts of organic acids
such as acetates, propionates, malonates, benzoates, and the like.
A thorough discussion of pharmaceutically acceptable excipients is
available in Remington's Pharmaceutical Sciences (Mack Pub. Co., N.
3. 1991).
[0232] Pharmaceutically acceptable carriers in therapeutic
compositions may contain liquids such as water, saline, glycerol
and ethanol. Additionally, auxiliary substances, such as wetting or
emulsifying agents, pH buffering substances, and the like, may be
present in such vehicles. Typically, the therapeutic compositions
are prepared as injectables, either as liquid solutions or
suspensions; solid forms suitable for solution in, or suspension
in, liquid vehicles prior to injection may also be prepared.
Liposomes are included within the definition of a pharmaceutically
acceptable carrier.
[0233] As is apparent from the claims, the invention also relates
to related embodiments to the treatment and prophylaxis disclosed
herein: the invention also includes embodiments where [0234] the
polypeptide of the invention is for use as a pharmaceutical, in
particular for use as a pharmaceutical in the treatment,
prophylaxis or amelioration of infection with A. baumannii; [0235]
the nucleic acid fragment of the invention or the vector of the
invention is for use as a pharmaceutical, in particular for use as
a pharmaceutical in the treatment, prophylaxis or amelioration of
infection with A. baumannii; [0236] the transformed cell of the
invention is for use as a pharmaceutical, in particular for use as
a pharmaceutical in the treatment, prophylaxis or amelioration of
infection with A. baumannii. [0237] the antibody, antibody fragment
or antibody analogue of the invention is for use as a
pharmaceutical, in particular for use as a pharmaceutical in the
treatment, prophylaxis or amelioration of infection with A.
baumannii.
Example 1
Immunization Study
Experimental
[0238] 16 individual proteins derived from A. baumanii (where 1
protein is a positive control) were tested. 16 mice were included
in each group. The study was divided into 4 separate experiments
comprising testing of 5 groups, that is 4 protein groups and 1
control group (adjuvant only). The 4 experiments are run in
parallel, that is staggered with 7-14 days between each
immunization. Hence the studies had a duration of 70-98 days
(.about.2.3-3.3 months):
[0239] Challenge strain: A. baumanii AB5075.
[0240] Mouse strain: C57BL/6 (inbred).
[0241] Dose: 25 .mu.g protein in each immunization.
[0242] Immunization route and interval: 3.times. subcutaneous with
14 days intervals.
[0243] Inoculation route (challenge): intranasal.
[0244] End point: Lethal challenge.
[0245] Adjuvant: Priming immunization: Alum+incomplete Freund's
adjuvant (IFA). 1st and second boost: Alum.
[0246] Bled and ELISA: Mice were bled 4 days prior to challenge and
ELISAs were run.
[0247] Mouse Tag: Each mouse was tagged, hence making it possible
to track the mouse-specific antibody titer with survival.
[0248] Trial type: Double blinded.
[0249] Number of mice per group: 16 mice.
[0250] Monitoring period: 7-10 days.
Experiment 1
[0251] Group 1 was immunized with the protein AB57_3582-22-253,
i.e. SEQ ID NO: 14, amino acid residues 22-253.
[0252] Study Group 3 was immunized with the protein
AB57_1088-22-159, i.e. SEQ ID NO: 9, amino acid residues
22-159.
[0253] Group 5 (the negative control) received phosphate buffered
saline (PBS).
[0254] Groups 2 and 4 were immunized with proteins irrelevant for
the present invention and did not provide protection. Data are
hence not shown.
Experiment 2
[0255] Group 1 was immunized with a protein consisting of amino
acids 2-346 of the protein having ATCC accession number 17978.
[0256] Group 2 was immunized with a cocktail of AB57_2465-45-550,
AB57_2465-551-906, AB57_1136-35-420, and AB57_1136-421-1071, i.e. 2
fragments of SEQ ID NO: 24 (amino acid residues 45 to 550 and 551
to 906, respectively) and 2 fragments of SEQ ID NO: 25 (amino acid
residues 35 to 420 and 421 to 1071, respectively).
[0257] Group 3 was immunized with a cocktail of the proteins
AB57_1893-26-711, AB57_1893-48-176, AB57_1893-478-711, and
AB57_1893-26-477, i.e. 4 fragments of SEQ ID NO: 20 (amino acid
residues 26-711, 48-176, 478-711, and 26-477, respectively).
[0258] Group 4 was immunized with the protein AB57_2233-22-162,
i.e. a fragment of SEQ ID NO: 10 (amino acids 22-162).
[0259] Group 5 (the negative control) received phosphate buffered
saline (PBS).
Experiment 3
[0260] Group 1 was immunized with the protein (AB57_3370-27-356),
i.e. a fragment of SEQ ID NO: 16 (amino acid residues 27-356)
[0261] Group 2 was immunized with a cocktail of the proteins
AB57_1059-1-754+AB57_1059-25-754+AB57_1059-25-466+AB57_1059-58-177,
i.e. the complete protein having SEQ ID NO: 23, as well a 3
fragments thereof (amino acid residues 25-754, 25-466, and 58-177,
respectively).
[0262] Group 3 was immunized with the protein AB57_1621-1-367, i.e.
SEQ ID NO: 17.
[0263] Group 4 was immunized with a cocktail of the proteins
AB57_3396-23-691+AB57_3396-306-691+AB57_3396-23-305, i.e. 3
fragments of a positive control (the protein having accession
number AO 41966).
[0264] Group 5 (the negative control) received phosphate buffered
saline (PBS).
Experiment 4
[0265] Group 1 was immunized with a cocktail of the 4 proteins
AB57_0478-1-550, AB57_0478-551-1110, AB57_2309-22-294, and
AB57_2309-1-294, i.e. 2 fragments of SEQ ID NO: 27 (amino acids
1-550 and 551-1110, respectively) and a fragment (amino acids
22-294) and the full-length version of SEQ ID NO: 15.
[0266] Group 2 was immunized with a cocktail of the 4 proteins
AB57_0053-19-108, AB57_1336-19-114, AB57_0830-1-166, and
AB57_3389-22-126, i.e. amino acids 19-108 of SEQ ID NO: 5, amino
acids 19-114 of SEQ ID NO: 6, the entire sequence SEQ ID NO: 11,
and amino acids 22-126 of SEQ ID NO: 7.
[0267] Group 3 was immunized with a cocktail of the 3 proteins
AB57_3081-2651-3047, AB57_0596-29-580, and AB57_0596-581-727, i.e.
amino acids 2651-3047 of SEQ ID NO: 30, and 2 fragments of SEQ ID
NO: 21 (amino acids 29-580 and 581-727, respectively).
[0268] Group 4 was immunized with a cocktail of the 2 proteins
AB57_3778-23-230 and AB57_1830-35-238, i.e. amino acids 22-230 of
SEQ ID NO: 12 and amino acids 35-238 of SEQ ID NO: 13.
[0269] Group 5 (the negative control) received phosphate buffered
saline (PBS).
Results
TABLE-US-00001 [0270] Group Survival Day 0 Day 1 Day 2 Day 3 Day 4
Day 5 Day 6 Day 7 Experiment 1 1 # Mice alive 13 13 2 2 2 2 2 2 %
Survival N/A 100.0 15.4 15.4 15.4 15.4 15.4 15.4 3 # Mice alive 15
15 0 0 0 0 0 0 % Survival N/A 100 0 0 0 0 0 0 5 # Mice alive 12 12
0 0 0 0 0 0 % Survival N/A 100.0 0 0 0 0 0 0 Experiment 2 1 # Mice
alive 12 12 3 2 2 2 2 2 % Survival N/A 100.0 25.0 16.7 16.7 16.7
16.7 16.7 2 # Mice alive 10 10 5 4 4 4 4 3 % Survival N/A 100 50 40
40 40 40 30 3 # Mice alive 13 13 0 0 0 0 0 0 % Survival N/A 100 0 0
0 0 0 0 4 # Mice alive 9 9 0 0 0 0 0 0 % Survival N/A 100 0 0 0 0 0
0 5 # Mice alive 13 13 2 1 1 1 1 1 % Survival 100.0 15.4 7.7 7.7
7.7 7.7 7.7 Experiment 3 1 # Mice alive 15 11 3 3 3 3 3 3 %
Survival N/A 73.3 20.0 20.0 20.0 20.0 20.0 20.0 2 # Mice alive 16
15 8 8 7 7 7 7 % Survival N/A 93.8 50.0 50.0 43.8 43.8 43.8 43.8 3
# Mice alive 16 13 0 % Survival N/A 81.3 0.0 4 # Mice alive 16 15 6
6 6 6 6 6 % Survival N/A 93.8 37.5 37.5 37.5 37.5 37.5 37.5 5 #
Mice alive 15 13 1 0 % Survival 86.7 6.7 0.0 Experiment 4 1 # Mice
alive 12 12 9 7 6 6 6 6 % Survival N/A 100 75 58 50 50 50 50 2 #
Mice alive 13 13 5 2 2 2 2 2 % Survival N/A 100 38 15 15 15 15 15 3
# Mice alive 10 10 5 2 2 2 2 2 % Survival N/A 100 50 20 20 20 20 20
4 # Mice alive 13 13 4 0 0 0 0 0 % Survival N/A 100 31 0 0 0 0 0 5
# Mice alive 13 13 1 1 1 1 1 1 % Survival 100.0 7.7 7.7 7.7 7.7 7.7
7.7
[0271] The above observations has let the inventors to the
following conclusions:
[0272] Proteins tested that provide significant protection against
challenge:
[0273] 1: AB57_1059-1-754, AB57_1059-25-754, AB57_1059-25-466, and
AB57_1059-58-177;
[0274] 2: AB57_3396-23-691 (positive control), AB57_3396-306-691
(positive controls, and AB_3396-23-305 (positive control);
[0275] 3: AB57_0478-1-550 and AB57_0478-551-1110;
[0276] 4: AB57_2309-22-294 and AB57_2309-22-294.
[0277] A number of proteins tested are found to possibly provide
protection against challenge infection:
[0278] 1: AB57_3582-22-253;
[0279] 2: AB57_2465-45-550 and AB57_2465-551-906;
[0280] 3: AB57_1136-35-420 and AB57_1136-421-1071;
[0281] 4. AB57_3370-27-356.
Amino Acid Sequences of the Proteins of the Invention:
[0282] In the present specification and claims, the amino acid
sequences of the proteins are identified via the SEQ ID NOs. set
forth in the sequence listing and the table below. However,
alternative designations are used in the examples, according to the
following table:
TABLE-US-00002 Designation: SEQ ID NO: AB57_1759 1 AB57_1009 2
AB57_1902 3 AB57_1614 4 AB57_0053 5 AB57_1336 6 AB57_3389 7
AB57_3578 8 AB57_1088 9 AB57_2233 10 AB57_0830 11 AB57_3778 12
AB57_1830 13 AB57_3582 14 AB57_2309 15 AB57_3370 16 AB57_1621 17
AB57_0504 18 AB57_0619 19 AB57_1893 20 AB57_0596 21 AB57_2870 22
AB57_1059 23 AB57_2465 24 AB57_0791 25 AB57_1136 26 AB57_0478 27
AB57_1048 28 AB57_3621 29 AB57_3081 30
[0283] When designating a fragment of one of these proteins, this
is done using the nomenclature AB57_XXXX-A-p1-p2, where XXXX is any
of the 4 digit numbers following "AB57" in the table above, and p1
and p2 are the start and end amino acids relative to the entire
sequence of the protein. For instance AB57_3081-50-200 is the
fragment of AB57_3081 that has the amino acid sequence defined by
residues 50 to 200 of AB57_3081.
TABLE-US-00003 SEQ ID NO: 1
MTQLINKGGFRERANRSRKYQQSENKQVALPSKKYQPQTKLQDNQSEMIQAKAGTAETSD SEQ ID
NO: 2
MKLAKTLLATTLALTAASTFAASKHDQAHNTAGEEKVVVSTQEQANTANAASDAVGSASEAAPATR
SEQ ID NO: 3
MIDEEKPLNFEDDDEPLDFEDEEFIDDKKEDEMYNSITKDGSSVDPADDGTRHIRPEDGDPIEIDE
SEQ ID NO: 4
MSTTNNQANQRNNQQQQQQQNDNRNQQQHGNQQQNDQQQQNNQQQQQNDNRGQQQGSNQKDSGQQNSNNNQQR
SEQ ID NO: 5
MSAKLVVTLLATSLLTVGCVAYTDDPYYRGGYGYHDHDDDRYDRNDGRRYSEWERKRWEERKRLYEQQRKDIRE-
QQKDR REWEKRHREWEKKRLEDRDHDHRDYRHDD SEQ ID NO: 6
MNKLLVALGLAATVALVGCNKDKAPETGATTGEHLENAAQQATADIKSAGDQAASDIATATDNASAKIDAAADH-
AADAT AKAAAETEATARKATADTAQAVENAAADVKKDAQH SEQ ID NO: 7
MKMTAKIALFSAAIVTMGSLAACQSTTQPPKPEHGMMQDGPRDGHHHRMKHREFTPEQKAAWEQHRAERKARFE-
QIQKA CEGKVVGQTVNVQVGDKTLEGTCNLRFEPKRPQPPVNAPAPVATQAK SEQ ID NO: 8
MKAIKILCITSSILVSSSLFAETPQPQQVNEATSKTMPYGDNPSLGRVLLYKTGKGIQNLGDSIQGASEKTSNK-
ISEKW KDTKEFTAEKAEVVQQKADTAKVFTEQKIEQAKQNITSSRNGENIPIEQGELSKSSTTAN
SEQ ID NO: 9
MKKSLLAIALMSTLLVACNKHENKTETTSDASTPVQTAQSNNNEAVDTAHTAENSLDWDGKYKGTLPCADCEGI-
KTELE
LKDDKTYELTETYLGKGDANPFETHGKFTFDKDNTSVITLDDKAQNRKFFIGENTATALDMEGKKVEGSLAEHY-
VLKKE D SEQ ID NO: 10
MANKKLLICAAIAAGLLLTACVKKETPKEEEQDKVETAVSEPQPQKPAKFESLESVDTQEAQVQEQPQVEVHRE-
ETANT
TTEIRRETRPARSDESSQTQVAEQPKSETPKVEPKPEKKPEPKAEPKPEKAQSKPAAKATEPANTEDDAVAAAI-
AAATP ALKN SEQ ID NO: 11
MTTENKLDELKANAADAKVQGEKALDDLKENVKEKQTAGKEAIADKVDELKTKAADAKVQGEKALEDLKENVKE-
KQAAA
KEAVEDKASDLKGKLDDAQHSLQDKFDHLRTEAAHKLDDAKAKAAELKEEAATKFDELKTQATAKFDELKKTAT-
EKLNK LKNHDSAE SEQ ID NO: 12
MHTRRILLAFSLAASAASVAFADYQNINQSTDSDRLEQLSKTLSQGSYTHPDDLDLPASAKVSVTLREKTVELN-
NDSLA
KKYGTTTAKNSFKTSSSNPYSWLVSHPLPDTVRVSSNFGGRTMGGRAEHHGGLDMAAPSGTPIYATGPGIVTKS-
GWGTG
YGQYVEINHGNGYLTRYAHASRLMVRVGDQVSAGDHIANVGCTGRCTGPHLHYEVVKDGQRKNPSTYLAMLP
SEQ ID NO: 13
MGMTFTDIENKSAKRLIGIAAVIFLHLLVAYILMSGLANNIQKPAEKPVELQIIQDIKPPPPPKPEEPKPKEKP-
PEPPK
MVEKVAKVPEPPKEVEKVATPVQKTTPVAQTTKVATPAPAAPSTPSPSPVAAPAPVAAAAPALKPAGVTRGVSE-
GSAGC
EKPEYPREALMNEEQGTVRIRVLVDTSGKVIDAKVKKSSGSKTLDKAATKAYSLCTFKPAMKDGVPQQDWYEIE-
YPFVI E SEQ ID NO: 14
MKMMKTAIVTASVLASASIFAQSAGVNAGASAQVNVQPGGLVSGVANTVKNTAHTVGNTAKHAGHVAADTTVKA-
TKKTT
GKVTELSSKAATGTKHVASEAVTGTKHFATEAATGTKNLATKAATGTKNLAVEAKADTKAHLDAVKTKVAEKQA-
DQKEF
TAEKQADAQARVDAVKARVAQNQAEQKEFVADTKADAQAKLNTAQPAHGVNAQTGVNVGVNVAGINANANVNAG-
AQAST QKGEKKSFIKGLFGTN SEQ ID NO: 15
MQMKKHSLLFIALMSTTSLYANIPIESRGLSQNDGSASNTSSSNISVPTNLNWELMQKNQQLENDIRTLRGQLE-
EQAND
IEQLKKDLANRYTDLDQRLELLHQKVDPDSATQDDSSNATSDNTTPASAPAPQTTESNKVAAVPATQTSEQQPS-
APTTT
TQPAPAAAQNQSNSLELEKAAYTVALDAYKQGGAKKAIAPMQNFIKNHPNSIYTGNAYFWLAEFHLATDPVNYN-
EAKKN YNVVANQYPNSSKAPRALYQLYSIAKDVDKNTVSANQYKNKLLSQYPKSEEAKFFNK SEQ
ID NO: 16
MSMNNKQRWMGGVVLLGGGVLLAALLLKGNEEIKQVDVQPQTSTSPKLQAKPKQSAQEGQMVQLQPLAVDVETE-
KRLLE
EQRRSREKAVAEQEARAAEFLAMQQQAEADAARKAAAEYAAINARRAAAQESSDNIPPEVAGSENKAKGQQTDT-
KKSVD
LAKADADKKAAEAKRLAEADKKAAEAKRQAEADKKAAEAKRQAEADKKAAEAKRQAEADKKAAEAKRQAEADKK-
AAEAK
RQAEADKKAAEAKRKAEAEKKAEAEKARELLENGDKKWMVQVALAANQANADAVVSKLRAKGYKVTTSPTSKGI-
RIMVG PAKDRDTADTTRKKITSDASLNMKSAWVIDWVPLDQRKSD SEQ ID NO: 17
MANTRYEDDNNSSGTSNRGFASMDPERVREIASKGGRAAHASGNAHEFTSEEAREAGRAAHASGNAHEFTSEEA-
REAGA
LSHKNDDRNGRGRSRYDDDEDDDRGRSSGRGRGRSRYDDDDEDDDRGRSGGRGRGRGRDDDDEDDDRGRSGGRG-
RGRSR
DDDDEDDDRGRSGGRGRGRSRRDDDDEDDDRGRSGGRGRGRSRRDDDDEDDDRGRSGGRGRGRSRYDDDDEDDD-
RGRSG
GRGRGRSRRDDDDEDDDRGRSGGRGRGRSRYDDDDEDDDRGRSGGRGRGRSRRDDDDEDDDRGRSGGRGRGRSR-
YDDDD EDDDRGRSGGRGRGRSRRDDDDDDDDRRGRSDGRGQNSRNQKRDAYGRFTS SEQ ID
NO: 18
MLYVIPFIILLVVAVILKKRENSQKQEATSPKNINRKSGKKASAKSSKSSREKIKAKVIEENIPAIPQSNPVPE-
ALRHN
IQQLIQEKQFSAAEAQVNQALKKDNTQHELYLLLLEIHIAQKDEFAIQQLISHIRSLGLNEIAAQAETRQKEYE-
SSSQP
DAIDFPQAQTYEEPKNTDTTAQFDELTTSSSEASFDDLQKDYTPVKQEPAIEIEPLEFNFSFEQNSATENTNQP-
AQQPE
LSSTQETNELADLEFSFDLAPLHETEEKSQAVEVKADQENSINALDFNFDLNPSSSETKSVQQAPSLDEIKLIE-
QAPLE
ATSIAPLEFSLDEPALVPAPELETQNHIDVVNEAATQTQIEDPLLEAFPELKQINENELDLKLAEQYIKFGANQ-
AARNL LQGDEQKFNTEQQQHAKNLLNRIAS SEQ ID NO: 19
MPKIKPIKLVIIVVCIAIIAVLAWKFLKPKQQQPQYITAEVTRGDIENNVLATGTLDATKLISVGAQVSGQVKK-
MYVQL
GDQVKQGQLIAQIDSTTQENSLKTSDANIKNLEAQRLQQIASLNEKQLEYRRQQQMYAQDATPRADLESAEAAY-
KTAQA
QVKALDAQIESAKITRSTAQTNIGYTRIVAPTDGTVVAIVTEEGQTVNANQSAPTIVKIAKLQNMTIKAQVSEA-
DIMKV
EKGQQVYFTTLGDETKRYATLRQIEPAPDSISSESNSTTSSTTSSAVYYNALFDVPNTDGKLRIDMTAQVYIVL-
NSAKN
ALLVPSSALSSKQFSGQRKQGQSADKASSTPSAERKHQGNGVRLERLNLTPEQKQLIEQGKATLSVVRVLQADG-
TTKPT QILVGINNRVNAQVLAGLKQGDQVVIADSSENSAASANSGNNRRRGPMGM SEQ ID NO:
20
MNIPPRPFKLSVIACAICYANLTYAQDAQVQALQTIQVKASNAEQSSEQTKAYNVKNSSSATKLNIEAKETPQT-
INVVT
RQQIEDFGLTSTRDVLRNTPGVTVSNQETERTTYMARGFEISNILTDGVGFPLSGYNYNNTNPDTYFYDRVEVV-
KGADS
LTNAFGDPSATINNIRKRPTQEFQASGGVSYGSWDTQRYEADVSGSILPSGKVRGRIMGYEQTGDSYLDRYSAE-
KNGFA
GIVEADLTDSTLLTAGYSQEQNKPNANNWGALPLLDANGKQISYDRSYNPNPDWAHWDNETQNAFVELKQKLND-
QWNAK
LTYNYLDTKHNSRLLYYYGYPKADGSGVSLTPWGGQEHQEKHAVDFNLEGTYKLFNREHEATLGYSYVRNHQQD-
KQSTG
TINDSNVIKSTTTDWASWTPQSITWSDFTEAANYKQNINSIYAATRLHLNEDLKLLLGANYVQAESKGESYSSP-
MSYSE
SKVSPYVGLTYNFTPEYTGYMSYTSIFRPQTGIDKDTNQALKPIEGKSYEMGVKSSWLDDRLTGTLSVFKTEQN-
NYPLR
NSDGNPLNRKVPTSDLESQGVEVGLSGQITDNVNLSFGYAQFSIKDTKNGGEARTYNPNQTLNLLTTYTPPVLP-
KLKVG
AGLQWQDGIKLYDSNVNGTIKQDAYALVNLMASYEVNDHITLQANGNNIFDKKYLNSFPDGQAFYGAPANYTVA-
VKFKY SEQ ID NO: 21
MKLQTIACAVAIATGGLFFSHTMNEARAATNTAAVSQSIQPTQEQALVARQLATLVDRQHYLNMRLDANTSNRI-
LDMYL
DSLDPDHSLFLDAEVQNYKKLYGSNFGASLKAGNLTGPFAIHQQYRERLKQFYEFMLAELKKPQNLKQPNTFIE-
VDREK
APYFKTSAEQQNHWRKMLVSQLINLTISREEEQAKQKALKENPSLADGQDLTGPEDLTPAQTLTKRYTRQLERI-
SRVKS
DDVLDKTLNAMLATYDPHSNYYPPIDAIELNRQTTLQLEGIGVSIRPERGNEDYTKIETIVEGGPASKSGQVKS-
GDRIV
GVAQEGGKMIDVVGWSSSEIVGLIRGKRGTKVTLKLLGAGASMSQARNVTLVRDVIQEEDAGVRSRTVEVTRDG-
KKHLL
GVIEIPSFYFDYRSRRAGQQYRSVSEDTANAFEALKAKKVEGIIIDLRNDPGGSLEEVARMLGQVIKSGPVVQI-
RDGNG
NVSVFEDNDGGQQIYTGPLAVLVNLASASASEIYSAAIQDYERGIIIGSTTTGKGTAQVQLDTLAYGQATLTQR-
KFYRV
TGGSTQNKGVVPDIKLVDIYNEEFGERKSKNALKWDTIPTAPFKREGSVQPYVAKLSQLSEQRVAVDPQFKYLN-
KRTAI
AKVTSDQKQVVLDIDKRRAELLSLEKQTLDAENERRIATGQKPFPNWESYQASLDALAESRAKMKANQRPALPE-
EETFV NEAANVLMDYAKLQNR SEQ ID NO: 22
MTRIIVASKEGLDVLQDGQLNKVVLNQPTIIQIGVSQKDIASMEKQGGSLVIHLKNGETIVLENFFNEATNTTE-
HSLVF
PTEQGKEVEAQFDAQGKVIDYRGLNHVTDLAYTSTSPSAATMAVDNDPSFSMGNVLKAGLAVLAAEGLYLWAFD-
KDDKD
DSPSTPDLIAPAAPTATLADDTVTVTGKTEANAKIYIKDAAGNTVASGVADASGNYTIKLDKPLVNGDKLNVIA-
QDAAG
NNSKVTVVTGTKDTIAPDVPQAQLSDDGSLLTGKAEANAKITVYDATGKVLGTVFANKDGIYSLKLTPPLTSEA-
GGKVV
AEDAAGNKSEEVKIIAGKDTIPPASPFVEVNKEGSVIHGKTEANAKVQIKDADGKVIGSGTADAQGEFQITLSP-
ALKEA
QKGTVVVEDAAGNVSKPVEITPGFDSIAPDKPTVQINTDGTSVTGTAEANAKIEIKDTTGKVIGSGTADANGKF-
TISIS
PALTDNKHASVSAIDNAGNKSEVVDIVGTKDTTPPAKPILNSVDDDVGAVKGAITAGSETDDARPKLTGSGEAN-
ATLTI
YDNGVAIGVVTVTSGRSWSFTFDKDLALGKHTITLTQTDAAGLTSEASSPFTFYVVAPKAASLSETSVDILSTE-
GPSLA
DSVGLHTLKVAQNTTTETNNPQKSVPLDDLLKSSTASESDPIAKLLSSTALKTTQASEPIEVNASVGQTTSNPN-
HPLPD TTSSVLQNLLDQTYPVV SEQ ID NO: 23
MSKRIIQSVLSVSVLASMMSMAFAAQNEQEQAEQTLEKPAEPVKLETIFVTAEEQVKQSLGVSVITKEDLEKLP-
VRNDI
SDYVRRMPGVNLTGNSATGQRGNNRQIDIRGMGPENTLILVDGKPINSRNSVRYGWKGERDTRGDSNWVPAEAI-
ESIEV
LRGPAAARYGSGAAGGVVNIITKKVTNETHGSVEFYTSQPEDSKEGSSNRVGFNVSGPLIKDVLSYRLYGNYNK-
TEADD
VDINKSIGSTAAGREGVKNKDISGRLAWQATDQQTVLLDISSSKQGNIYSGDSQLNANAEADAILSQLIGKETN-
TMYRD
SYALTHEGDWSWGKSKLVAQYDKTHNKRLPEGLAGSVEGKINNLDDKATSRLETLRFNGEANIPFEYYLPQVLT-
VGTEW
VEDRFKDNVSTTQGKDSSGSGYGDQLAKGDRSKMESRIASAYIEDNLKVTDSTDVVLGLRFDDHSKSGSNWSPS-
LNITQ
KLNDNFTLKGGVAKAYKAPNMYQNAEGYLLSTNGNGCPANIESRCLLQGNGDLKPETSVNKELGIQFQRDIVNA-
SLTWF
RNDYKDKIVAGTHVVGTVDGSSTNANTGAVTNTKWNILRWENTPKALIQGFEGSLGLDFGDIRWTNNFTYMMDS-
KDKQT
GNPLSLVPIYTINSIFDYDITDQLDVNFVFTQYGRQKSRQFAENRLESGIGSGGANSALKPSTVKSYSTAGINV-
GYKFS DQISTRVGVSNLFDKQILRDSNSISQTYNEPGRAYYASLKYSF SEQ ID NO: 24
MPSKIKFKQSTLSHSMHLILKMQSIPKLICSSLLLSLCVTPCYAQSSAETVIPEANQTVTDSLVQQTNTNNPSD-
VPITD
VATLVTQAQQQQDSLAILQQQEQFPNQIEEFKPITLDNLEDLPVMPVDQNMANEIYRVAEEAKNEAQNFQNGTQ-
KQPEM
VVSDASQAELHEINQAPVNIDQLMHEIQSDSKIVVEANETGKTLPELTAAVEEPPEEKGFFRRIFNKIRPPRVI-
PMEQI
PRITAEVTGAPDDLAKNIKGKLSTFTQESFEDFNAALPQLRSLSNQAAQAVGYYNAEFRFEKLSASRVRVNVTP-
NEPVR
INEQNIEFTGAGAKQPQFQVIRLVPDQDVGDIFNHGLYETTKSRIVDAASDNGYFDAYWRLHDVKVSQPENKAD-
INLKY
ETGERYKLGKVEFRMSDPSKPLPLNMNILESMAPWKEGDDYAFWRVNVLANNLTNSRYFNYTLVDSIKPDPIEK-
PLELP
PDLQALVDQQNVDIDESKLLPLEQQQLAKARQLASSSKEVTQNVVDEKQFAGTESVQAAPASLKAATVQHEEQE-
SEQDR
LQAQAREEKRIPVIVTLNADKLNSLETGIGYGTDTGARLRSQYRRSIVNKYGHSFDANLELSQIRQSIDGRYSI-
PYKHP
LNDYFNIVGGYERETRDDIGPDVSLLTESAVLGGERVIKKPLGNWQHTIGVRYRLDRLTQKGNVDISELPDAFK-
TAASE
QEALLFSYETSKTSSNTRLNPTKAFKQTYKLELGSESLLSDANMAIATAGWRFIYSLGENDDHQFVGRSDFSYI-
FTDEF
DKVPYNLRFFTGGDQTIRGFDYKSLSPEDNGYKIGGQALAVGSLEYNYQFKEGWRAAVFSDFGNAYDKSFSNPT-
AYSVG VGIRWKSPIGPIRLDVASGISDDNHPIRLHFFIGPQL SEQ ID NO: 25
MFIKSILSSITSIIPLPENSNTSSNLGNGSGDGLLNGISSGNGEHNYGIGNGIADDASITAPITIPLNLSGNSI-
TLIGN
SSSSSVNSSPTTTSNNVNDNDVTNNGNGSTIGSGTGNGSGDGLLNGAASGNGEHNYGIGNGIADDASITAPLSI-
PINLA
GNSITLIGDSSSSSVNNSATNTSNTVNDNDTTYNGNGSGGGNGSGDGLLNGIGSGNGEQNYGIGNGIADDASIT-
APITL
PINLSGNSITLIGNSSASSVNSSPTTTSNTVNDNDTTYNGNGTGDSGVSALGGSGNGSGDGAGNGIASGNGEHN-
YGIGN
GNGDDVDITAPITGVLNISGNSFTLIGNSSSSSVNTAPTTTSNTVNDNDTIDNGNSGGTGSGSGNGSGDGLLNG-
AASGN
GEHNYGIGNGNGDDVDITAPITGVFNFSGNSFSIIGNSSSSSINTAPTTTTNTVNDNDVTDNGNDGGGLVGGSS-
GNGSG
DGLLNGAASGNGEHNYGIGNGNGDDADFTFPLTGVLNFSGNSLSGFGSSSSDSVNVAPTTATNTVNDNDTIDNA-
NTGGL
GDGSGNGSGDGLLNGAASGNGEHNYGIGNGNGDDADFTLPFTGGLNILGNALSGIGGSSTDSINISPTTTSNTV-
NDNDT
TNNGNTSGGVIGSGDSGNGSGDGLLNGISSGNGEHNYGIGNGNGDDVDVVAPITTPLNVLGNSFSFIGGEGTGD-
ILGPI
TGIIGGIGGDGDILSPITGIIGGIGGDGDILSPITGIIGSIGGIGGDLGDNPLTGIIQSGIDVLQNLESLKTGL-
INTGI
DTIAGTIIGVFPDAEHPVGDFADLGKLLFETSRDSVNGTLEAISDLAGADLEGASGSITGVIDTLITNGSTAST-
IIQHI
VGDDLVTENGGLLGSITTIIGGVDSGDGGLLGGLDGLISINYGDSDNSNSIDVEDILGNILGSVGSNQGIAVGE-
PDPTG GSLIHTISLNTVNQLTDQLLHALPTV SEQ ID NO: 26
MYKPTTFVWQPSAASLFKITVLSSALAALGITTGCSSTPQSAKTSKTKQVSGAGYLDASSLDSLEDLLSATDMR-
AVEGD
RLLILKHGDVWKRMAVGFKMDLNHWDPRIEAQRSWFISRQPYLDRLSARASRYLYHTVKEAERRGLPTELALLP-
VIESS
YDPAATSSAAAAGLWQFIPSTGRIYGLQQTGMYDGRRDVVESTRAAYEFLGSLYNQFGSWELALAAYNAGPGRI-
QQAIN
RNQAAGLPTDYWSLKLPQETMNYVPRFLAVAQIIKNPRAYGVSLPPIANRPHFREVTLSAPLSLNEIASVTGLS-
RAELY
ALNPGYRGETVDPASPMRILIPADISPSVDNKLKGMKAGGSSGWWASVTSPSKPTTTTSTSVTVRTTPSTPAQP-
VRPST
PAKTSSSSVTVKTTTPRGSDALAAFAASADVPSAPRIPVAVTPAANIKPVRTEPPISATEREKILAAVRAEGEK-
ETVDQ
ALEPQATQAEKDQVVAELKALAPQGTEIVDPYDGKIKLTAIQTSQSVAEQQGKEVSKGFAYPKTLAEDATLANS-
EDAQR
NKDKPYIKTDTDVVVVQPKGKRSTYTVQPGDTLAVIAMKNGVNWRDVAKWNQIDPEKTLFVGTSLYLYDAKPQE-
AETTA
KSAAKPDVYVVQANDSLTGVANQFNLSVKQLAEYNDLSVTDGLFVGQKLQLKEPKGNRAAKVEPKAIQASTRRI-
ATKSY
TVKRGEYLKLIADRYALSNQELADLTPGLSAGSNLIVGQKINVPAKEITVDEVDDSKASGKYEKLAAGPSYKTE-
SYKVQ
RGDTLSSIATKSKISLAELAELNNLKANSHVQLGQTLKVPAGASVPDQYVVQSGDSLNAIAAKYNLQTSYLADL-
NGLSR
TAGLRAGQRLKLTGEVETTSKVSAKNTKEETPETYTVKSGDSLGNIANRYHLQLDYLAALNGLSRNSNVRVGQR-
LKLTG
DLPTVETAKTDTAKSSPKAVVAGKNTEKYTVKAGESLNAIASRAGISVRELAEMNALKANANLQRGQNIVIPKT-
VVEYK VKRGDTLIGLASKYGLETTLLAELNNLTPSTQLRIGDIIKVPNL SEQ ID NO: 27
MKRMLINATHAEEVRVALITGNRLYDFDLENRTREQKKSNIYKGHVTRVEPSLEAVFVEYGAGRQGFLSMREIA-
NSYFQ
ADPRQTSNIRELITEGTELLVQVEKEERGNKGAALSTFISLAGRYLVLMPNNPKGGGISRQISGSVREELKEIL-
ASLNV
PRGMSVIVRTAGIGRTQEELQLDLQHLLDLWAQIQGTASSGPSPMLVHQEAGVVTRAIRDYLRDDVAEILIDSE-
QAYNE
AYNFVKAVMPRQLDKLKTYTLNEPLFAHFGIESQIQTAYEREVKLPSGGSIVIDQTEALVSIDINSAKSTRGHD-
VEETA
LNTNLEAAEEIARQLRLRDIGGLVVIDFIDMTKERNQRMVEAKLREATQSDRARIQFGQLSRFGLMEMSRQRLR-
PSLEE
ATGYVCPRCHGTGMVRDLRSLSLSIMRKVEEIALRERHGEVQVEVPVEIAAFLLNEKRHSLVYLEQTSGVRVTV-
LPHPH
LETPHYEIAYNPDGFAPSSYERTEATRSSEKELGYESSEWHLEEADHGHAHVTATASTHAAAQKKANHATQPVA-
QPSAQ
KAASPCAWLENLFVQKQAQTVDQSRSAQNAAAAIEQMVNTGAVSRGQFGQVAVPAVAEVAPVQSNNAYISQSPV-
KQDVR
EHVEKDDKSQQQRQNNKKRKHKEQREQHHQSHEQQHQVHEEVVQLSRQEQRELKRQQKRQQQQDQQHQNNDVQH-
TENAV
PRRDRNNQQRPNRPNRHRDPSVLNENQNTLVVVDEKQIKVDVIDAPKHDVMNTALIINVDQGQSEIVALTPERR-
HVERV
ETTSTEVAQEPTPAPVVAEKAAVVETKEEAQPSQEAAQPQIKRASNDPRMRRRQQREAKHAKAATPSIAPSQIP-
TLAQH
TIGSLIRHVYGEDCTVLIEQFGLVPTFNRALQKFAEQYASTLVVEVTAETEEKKPVTRDAELPSHKPAEEAEPA-
PVLPL
TPPQAPAPRVANDPRERRRLAKLAAEQAFEQVKQQHSAQEEVATPAPVAEETVAAPTAETQATVEPAQQPLELN-
QSTEV
VQPEAAPAEEKATEETVAEAPAAKEPAPSKAASKAKAAAEETVAPTEATTDAESEDVKADKDKPSRPRRPRGRP-
PKKAN PVAE SEQ ID NO: 28
MSTLATLKALLAKRILIIDGAMGTMIQRHKLEEADYRGERFADWAHDLKGNNDLLVLTQPQIIQGIHEAYLDAG-
ADIIE
TNSFNGTRVSMSDYHMEDLVPEINREAARLAKAACEKYSTPDKPRFVAGVLGPTSRTCSISPDVNNPAFRNISF-
DELKE
NYIEATHALIEGGADIILIETVFDTLNCKAAIFAVKEVFKQIGRELPIMISGTITDASGRTLTGQTAEAFWNSV-
RHGDL
LSIGFNCALGADAMRPHVKTISDVADTFVSAHPNAGLPNAFGEYDETPEQTAAFLKEFAESGLINITGGCCGTT-
PDHIR
AIANAVKDIAPRQVPETVPACRLSGLEPFNIYDDSLFVNVGERTNVTGSKKFLRLIREENFAEALEVAQQQVEA-
GAQII
DINMDEGMLDSQNAMVHFLNLVASEPDISRVPIMIDSSKWEIIEAGLKCVQGKPVVNSISLKEGYDEFVEKARL-
CRQYG
AAIIVMAFDEVGQADTAERKREICKRSYDILVNEVGFPAEDIIFDPNVFAVATGIEEHNNYAVDFIEATGWIKQ-
NLPHA
MISGGVSNVSFSFRGNEPVREAIHSVFLYHAIKQGMTMGIVNAGQMAIYDDIPTELKEAVEDVILNQNQGESGQ-
AATEK
LLEVAEKYRGQGGATKEAENLEWRNESVEKRLEYALVKGITTYIDQDTEEARLKSKRPLDVIEGPLMDGMNVVG-
DLFGS
GKMFLPQVVKSARVMKQAVAWLNPYIEAEKTEGQSKGKVLMATVKGDVHDIGKNIVGVVLGCNGYDIVDLGVMV-
PCEKI
LQTAIDEKCDIIGLSGLITPSLDEMVFVAKEMQRKGFNIPLLIGGATTSKAHTAVKIDPQYQNDAVIYVADASR-
AVGVA
TTLLSKEMRGAFIEEHRAEYAKIRERLANKQPKAAKLTYKESVENGFKIDESYVPPKPNLLGTQVLKNYPLATL-
VDYFD
WTPFFISWSLTGKFPKILEDEVVGEAATDLYNQAQAMLKDIIDNNRFDARAVFGMFPAQRTDADTVSVFDEAGQ-
NVTHT
FEHLRQQSDKVTGKPNLSLADYIRADREQQDYLGGFTVSIFGAEELANEYKAKGDDYSAILVQSLADRFAEAFA-
EHLHE
RIRKEFWGYKADEQLSNEELIKEKYVGIRPAPGYPACPEHSEKAVLFDWLGSTDKIGTKLTEHFAMMPPSSVSG-
FYYSH
PQSEYFNVGKISQDQLEDYAKRKGWTLDEAKRWLAPNLDDSIV SEQ ID NO: 29
MKLKLKNFKPNNLWYAVCSSSMIFTWLMTSSVVQASDLQIYASPTAGKKTIVMMLDTSGSMTNNSYGENRLAML-
KNGMN
AFLASNNPVLNDTRVGLGNFSANGDSRSGQILVAAAPLGDASTLNTVGSQRYKLKQAVANLTAGGSTPSAHAYA-
EAAAY
LMGTTTYSETNYAIRKDSYIKRVRRSDNRTEYSYCTNYRDSQIDTANLWQPCRSNSYWSSWSTNNPGVDNATAY-
DTSSD
WTYYYTYYYTTFNYAVANADSGIPKSKSNDTASNPNIVVDRNATNSNAVYQSPLPAVANRQSCDGQGIYFLSDG-
EPNNT
TNTRSASVMSTALGSTFGADFNCSGGLSNTTADSGWACMGEFAKRLFDKTKNPAGVSIQTAFVGFGSDFSSLNS-
SDVKN
ACRLSSRTQSDRKGDDACSPNQSTNAVAAPGYGNGGFFPTQSSQGVTDSVIAFINNLDKVPLEPLTTGAISVPY-
DALNP
KNLQEYGYLRAFEPNPANTYLTWRGNLKKYHVVLSGANAGAFEANSGGLVYNASGAFRTGTKDYWNSSTYTDGG-
KVFLG
GSYANVPLPIAGQPETRDAEGNITKYYYAVQSKIRNLFTDVSAVAADGSLTKISTSGTNLLKIPAAPPEETNPF-
DTVAN
TASYVLGKFDPSTGQNILKAFPISLKLKILNYLGYSTDINATTLPSSLVTSNEPYLSMGGSIHSLPVQLTYNGT-
LDDNG
NLTSAREQSILYGTMEGGLHIVDASSGIEQMVFVPADILNDSVASKALVVGQSDASAPAHGMDGAWVSDPAYNI-
TTVGS
GSSAVSKVTAKQMNIYGGMRMGGSSYYGLDVLSPTSPKLLFRIGADQNDYSRMGQSWSKPVLANIRYNGSIRRV-
LIVGG
GYDQCYEKPNITLTDACFTNGKAKGNAVYIIDAKTGQRLWWTSDTGSNTDNANMKHSIVSRISTLDRDADGLVD-
HLYFG
DLGGQIFRVDLNNNQTKTNSTYSSFGVRVVRLANLATNDSTYDGTNDYTGGNAPRFYEPPTVTIHDYGIHTFIT-
VGIAS
GDRSTPLDVYPLTGREGMTPASALSGRPVNNVYGIIDRDFVKKNLMSLTDNQLETKDITRTGLRKNPQILRTGE-
TRVAQ
IFFPTTGVGKGGWYRSLSSTSDGTEKANNSFRIKGGLKAFEEPMAITGNLIILVYDPQGTGIVAADPCLPRVVG-
ETDRQ
TYCLPFGACLNSDGSIDQNKENHSGFETQTGTNCPVGASECNKNVIGSGIRSVTFVPTEDNPPTTNSCGKLKLS-
GNEQG TGQWQCTSHLVPTRWYERYR SEQ ID NO: 30
MTDAAGNTSEQAVQKVVVDTTAPQAGELTLSDLSDTGISATDQITQDKNFNLKLEGQESGSRVTYLVSTDEGKT-
WQETT
IAQKDLTDGVYQYKAVVTDAAGNTSETAVQKVVVDTTTPQAGELTLSDLNDTGVSVTDQITQDKNFNLKLEGQE-
TGSRV
TYLVSTDEGKTWQETTIAQKDLADGVYKYKAVVTDAAGNTSETAVQKVVVDTTAPQAGKLTLSDLNDTGVSATD-
QITQD
NSFTLKLAQPIVIGEQAALLDHYEVSKDEGKTWQETTADQKDLADGIYQYKAIVTDLAGNISESAIQKVVVDNS-
LNVES
TTVIVKPITEDNTISLVEKDQVISIRLEIANLPTDLNSSLTSVNTTLGNVTYNFHFDEVTQEWVTEIPAEFLWS-
VEPQT
NISIEISLTDQAGNTAIIKHTQNYNVDHTPNSPTLDSLTFNNIDGAIISGSAYKGSKVDIYNKNGDWLASTITN-
EEGKF
TLQDLSINSNQEVYAVATYNGYSSENSSIGLVTEVPAISITRISPEGVISGYATEGSHFIVKDQNGNILQEFNS-
NVFDS
SGITPFSVMALGEVRPFILSLDQPLEEGAQIIISIDKDNISGHPQYITADYTPAVFLETPQFDISGETLSVHVN-
EPNSF
IRAFSGEGNLIATGFTDEQGFASLQVFQFLKEGETVSVQVVDKNQNTSETLIEVPNFAYIPHVERITQEGLISG-
VAEDN
STVIVRDADGNELGKVTLGDDNSWSDFSHFSLSVNRPLIDGEKISVQIIDNKGLMSPEQNIIVDLTPPPAPTEL-
NFNDA
GDLVYGHAEPFSEILVKDGQGNILNKWFWNNWTDESGSFSIELGTFLTNAETVYVTATDVNGNVSLAAQIQAPN-
YAFAP
YVDSFTSDGVISGQAENNSTLVVKDAKGDVVAEIKVGEDNGWNGSSYFKLQLDRPLVDGEQFFLSIKDARGQVS-
ADTVI
TADTVAPTPASNLVFSEDGSYLTGVAELNTTIQVFDHNGQLVNIWNNTINSDGTFTIYLGSNNLHGEAFTVTVK-
DQAGN
VSEAISINAPLDDIAPNPIKNILLDANGQNFTAQAEANSQIEVFDSLGNQTGWGSTDSAGNVSGSFNQTYLHGE-
ELTFV
VIDRAGNRSIEFKQNALIDTIAPNPIANIIFNEDGQSFTAQAEAGSSIDVLDQTGNKIGFGYTDSSGNVSGYFQ-
QVYLH
GEELTFVVIDRAGNRSAEVKQSALNDDVVPNPIENIVLDLNGQNFTAQAEANSQIEIKNNNGDVVGYGSADSAG-
NVSGY
LYQVHLHGEELTFIVVDRAGNRSTEVKQNALIDDIAPNPIENIVLDINGQNFTAQAEANTQIEVKNAVGEIVGL-
GYVDG
AGNVSGYLYQVYLHGEELTFVVVDRAGNRSTEVKQNALIDDIAPNPIENIVLDINGQNFTAQAEANTQIEVKNA-
VGEIV
GLGYVDGAGNVSGYLYQVYLHGEELTFVVVDRAGNRSTEVKQNALIDDIAPNPIENILLDANGQNFTAQAEANT-
QIEVK
NTAGEVIGSGSTDSMGNVSGYFYQVYLHGEELTFVVVDRAGNRSTEVKQNALIDDIAPNAIENIIFNENGQNFT-
AQAEA
NSKVEVKNAAGEVVGSGYVDSVGNVSGYLNQVYLKGEELTFVVIDQAGNRSIEVKQTAFLDNTAPENATNLVFS-
EDGSY
LSGMAEPNATIQIFDQYGQLLNQWNNNVNWDGTFNIYLNSNYMHGEVFKVVVVDHAGNLSGEVTVKAPLDDIAP-
VAASD
LVFNEDGSSLSGVAEPNTFIQIFDQNGQQMNTWSQSVNADGTFTIFFGTYNLHGEEFTVIVKDLAGNVSEAVSV-
KAPLD
DIAPKPIKNIVFDANGQSFTAQAEANSQIEIFDSFGSQIGWGSTDSTGSVTGYFYQVYLHGEELTFVVIDRVGN-
RSDEM
KLNALMDTIAPKPIENIIFNENGQNFTAQAEANSFISVKNAAGEFVGYGYVDSTGNVSGHFNQVYLKGEELTFI-
VIDKA
GNQSIEYKQNALTDDIAPNPIENIVLNKNGQNFTAQAEADSQIEVKNTAGEVVGSGYVDSIGNVSGSFNQVYLH-
GEELT
FVVVDRAGNRSTEVKQNALIDDIAPNQIENIVFDVNGQYFTGHAEADTRIEVLDQFGNRAGWGYVDSQGNVIGY-
FNQVY
LHGEELTFIVVDIAGNRSVEVKQNALIDNVAPPAAANITLTSDGLLFGEAEPNSTVEIIDQYGAVITTTYVWYD-
GTFNQ
WINLSQYQTQNLSIVVKDQAGNRSEVVHELVPVFTNSPIAATELKLDIDGHILTGKATVGMSVVVTSTDGQTIN-
GGWNN
AVNEDGSFAIQLNDYYLQGQTLQVRVYDQNTNQYSLISEIIAPLDNIAPVINEVVINNDGYGITGQTDSKAIIQ-
VMDAD
GDLRAEFQADETGYFNASIYPPILRGEQLFITAIDLAKNISKPFNITFNADTNAPPSAEHIVVSENGFFIEGTA-
VAIST
VHIFDVHSNHVATNVADEAGNFNIQLYPPLASGQILRIVVEYNGYQSAYTEITAPIDTVAPNAATQLLLEDGNV-
LSGQA
EAYSIVNIFDANNNLVGQTNVGSDGAFLTHLWYEYWHGETLTVKVVDANQNVSVGTTIVAINDTVVPDVVTQLA-
IDEWG
SLTGRVESYATVELTYHFTDQPLSVTSTTALANGMFFIYLDRNATSLDLTVIDRAGNRSETISQIISDLPTVII-
DHFKG
DATDNTYNIDTIDDFVQEYIVEPYAIYKDVWIDNSYMYSDWVIEGHYEQIWFVDGYYESQWATSGYSTVQNIYQ-
NQNGI
TYIDNGTADSDYSRYEQQYYDFVNGQWQEGYELTYIRSEEGWVDTSHYEDVYIDTSHYEEVWVDTSHYQDIWVE-
NSYWE
SQLVESGRRDVDLGGHDKIISSVNYSLVGLYQTVNDPTTVDSFLESGRYVEDLELVGSAHLNATGNALDNLLTG-
NSGNN
VLNGREGNDTYITNEGTDTIVFQLLNSQDATGGNGHDTVLDFTLGDIRTNLQADKIDLSELLIDYSKDVSALAK-
FITVE QDAGNTTISLDRDGEGTMFNSVSLLTLNQVNTTLDELLNNQQIIV
Sequence CWU 1
1
90160PRTAcinetobacter baumannii 1Met Thr Gln Leu Ile Asn Lys Gly
Gly Phe Arg Glu Arg Ala Asn Arg 1 5 10 15 Ser Arg Lys Tyr Gln Gln
Ser Glu Asn Lys Gln Val Ala Leu Pro Ser 20 25 30 Lys Lys Tyr Gln
Pro Gln Thr Lys Leu Gln Asp Asn Gln Ser Glu Met 35 40 45 Ile Gln
Ala Lys Ala Gly Thr Ala Glu Thr Ser Asp 50 55 60
266PRTAcinetobacter baumannii 2Met Lys Leu Ala Lys Thr Leu Leu Ala
Thr Thr Leu Ala Leu Thr Ala 1 5 10 15 Ala Ser Thr Phe Ala Ala Ser
Lys His Asp Gln Ala His Asn Thr Ala 20 25 30 Gly Glu Glu Lys Val
Val Val Ser Thr Gln Glu Gln Ala Asn Thr Ala 35 40 45 Asn Ala Ala
Ser Asp Ala Val Gly Ser Ala Ser Glu Ala Ala Pro Ala 50 55 60 Thr
Arg 65 366PRTAcinetobacter baumannii 3Met Ile Asp Glu Glu Lys Pro
Leu Asn Phe Glu Asp Asp Asp Glu Pro 1 5 10 15 Leu Asp Phe Glu Asp
Glu Glu Phe Ile Asp Asp Lys Lys Glu Asp Glu 20 25 30 Met Tyr Asn
Ser Ile Thr Lys Asp Gly Ser Ser Val Asp Pro Ala Asp 35 40 45 Asp
Gly Thr Arg His Ile Arg Pro Glu Asp Gly Asp Pro Ile Glu Ile 50 55
60 Asp Glu 65 473PRTAcinetobacter baumannii 4Met Ser Thr Thr Asn
Asn Gln Ala Asn Gln Arg Asn Asn Gln Gln Gln 1 5 10 15 Gln Gln Gln
Gln Asn Asp Asn Arg Asn Gln Gln Gln His Gly Asn Gln 20 25 30 Gln
Gln Asn Asp Gln Gln Gln Gln Asn Asn Gln Gln Gln Gln Gln Asn 35 40
45 Asp Asn Arg Gly Gln Gln Gln Gly Ser Asn Gln Lys Asp Ser Gly Gln
50 55 60 Gln Asn Ser Asn Asn Asn Gln Gln Arg 65 70
5108PRTAcinetobacter baumannii 5Met Ser Ala Lys Leu Val Val Thr Leu
Leu Ala Thr Ser Leu Leu Thr 1 5 10 15 Val Gly Cys Val Ala Tyr Thr
Asp Asp Pro Tyr Tyr Arg Gly Gly Tyr 20 25 30 Gly Tyr His Asp His
Asp Asp Asp Arg Tyr Asp Arg Asn Asp Gly Arg 35 40 45 Arg Tyr Ser
Glu Trp Glu Arg Lys Arg Trp Glu Glu Arg Lys Arg Leu 50 55 60 Tyr
Glu Gln Gln Arg Lys Asp Ile Arg Glu Gln Gln Lys Asp Arg Arg 65 70
75 80 Glu Trp Glu Lys Arg His Arg Glu Trp Glu Lys Lys Arg Leu Glu
Asp 85 90 95 Arg Asp His Asp His Arg Asp Tyr Arg His Asp Asp 100
105 6114PRTAcinetobacter baumannii 6Met Asn Lys Leu Leu Val Ala Leu
Gly Leu Ala Ala Thr Val Ala Leu 1 5 10 15 Val Gly Cys Asn Lys Asp
Lys Ala Pro Glu Thr Gly Ala Thr Thr Gly 20 25 30 Glu His Leu Glu
Asn Ala Ala Gln Gln Ala Thr Ala Asp Ile Lys Ser 35 40 45 Ala Gly
Asp Gln Ala Ala Ser Asp Ile Ala Thr Ala Thr Asp Asn Ala 50 55 60
Ser Ala Lys Ile Asp Ala Ala Ala Asp His Ala Ala Asp Ala Thr Ala 65
70 75 80 Lys Ala Ala Ala Glu Thr Glu Ala Thr Ala Arg Lys Ala Thr
Ala Asp 85 90 95 Thr Ala Gln Ala Val Glu Asn Ala Ala Ala Asp Val
Lys Lys Asp Ala 100 105 110 Gln His 7126PRTACINETOBACTER BAUMANNII
7Met Lys Met Thr Ala Lys Ile Ala Leu Phe Ser Ala Ala Ile Val Thr 1
5 10 15 Met Gly Ser Leu Ala Ala Cys Gln Ser Thr Thr Gln Pro Pro Lys
Pro 20 25 30 Glu His Gly Met Met Gln Asp Gly Pro Arg Asp Gly His
His His Arg 35 40 45 Met Lys His Arg Glu Phe Thr Pro Glu Gln Lys
Ala Ala Trp Glu Gln 50 55 60 His Arg Ala Glu Arg Lys Ala Arg Phe
Glu Gln Ile Gln Lys Ala Cys 65 70 75 80 Glu Gly Lys Val Val Gly Gln
Thr Val Asn Val Gln Val Gly Asp Lys 85 90 95 Thr Leu Glu Gly Thr
Cys Asn Leu Arg Phe Glu Pro Lys Arg Pro Gln 100 105 110 Pro Pro Val
Asn Ala Pro Ala Pro Val Ala Thr Gln Ala Lys 115 120 125
8139PRTAcinetobacter baumannii 8Met Lys Ala Ile Lys Ile Leu Cys Ile
Thr Ser Ser Ile Leu Val Ser 1 5 10 15 Ser Ser Leu Phe Ala Glu Thr
Pro Gln Pro Gln Gln Val Asn Glu Ala 20 25 30 Thr Ser Lys Thr Met
Pro Tyr Gly Asp Asn Pro Ser Leu Gly Arg Val 35 40 45 Leu Leu Tyr
Lys Thr Gly Lys Gly Ile Gln Asn Leu Gly Asp Ser Ile 50 55 60 Gln
Gly Ala Ser Glu Lys Thr Ser Asn Lys Ile Ser Glu Lys Trp Lys 65 70
75 80 Asp Thr Lys Glu Phe Thr Ala Glu Lys Ala Glu Val Val Gln Gln
Lys 85 90 95 Ala Asp Thr Ala Lys Val Phe Thr Glu Gln Lys Ile Glu
Gln Ala Lys 100 105 110 Gln Asn Ile Thr Ser Ser Arg Asn Gly Glu Asn
Ile Pro Ile Glu Gln 115 120 125 Gly Glu Leu Ser Lys Ser Ser Thr Thr
Ala Asn 130 135 9159PRTAcinetobacter baumannii 9Met Lys Lys Ser Leu
Leu Ala Ile Ala Leu Met Ser Thr Leu Leu Val 1 5 10 15 Ala Cys Asn
Lys His Glu Asn Lys Thr Glu Thr Thr Ser Asp Ala Ser 20 25 30 Thr
Pro Val Gln Thr Ala Gln Ser Asn Asn Asn Glu Ala Val Asp Thr 35 40
45 Ala His Thr Ala Glu Asn Ser Leu Asp Trp Asp Gly Lys Tyr Lys Gly
50 55 60 Thr Leu Pro Cys Ala Asp Cys Glu Gly Ile Lys Thr Glu Leu
Glu Leu 65 70 75 80 Lys Asp Asp Lys Thr Tyr Glu Leu Thr Glu Thr Tyr
Leu Gly Lys Gly 85 90 95 Asp Ala Asn Pro Phe Glu Thr His Gly Lys
Phe Thr Phe Asp Lys Asp 100 105 110 Asn Thr Ser Val Ile Thr Leu Asp
Asp Lys Ala Gln Asn Arg Lys Phe 115 120 125 Phe Ile Gly Glu Asn Thr
Ala Thr Ala Leu Asp Met Glu Gly Lys Lys 130 135 140 Val Glu Gly Ser
Leu Ala Glu His Tyr Val Leu Lys Lys Glu Asp 145 150 155
10162PRTAcinetobacter baumannii 10Met Ala Asn Lys Lys Leu Leu Ile
Cys Ala Ala Ile Ala Ala Gly Leu 1 5 10 15 Leu Leu Thr Ala Cys Val
Lys Lys Glu Thr Pro Lys Glu Glu Glu Gln 20 25 30 Asp Lys Val Glu
Thr Ala Val Ser Glu Pro Gln Pro Gln Lys Pro Ala 35 40 45 Lys Phe
Glu Ser Leu Glu Ser Val Asp Thr Gln Glu Ala Gln Val Gln 50 55 60
Glu Gln Pro Gln Val Glu Val His Arg Glu Glu Thr Ala Asn Thr Thr 65
70 75 80 Thr Glu Ile Arg Arg Glu Thr Arg Pro Ala Arg Ser Asp Glu
Ser Ser 85 90 95 Gln Thr Gln Val Ala Glu Gln Pro Lys Ser Glu Thr
Pro Lys Val Glu 100 105 110 Pro Lys Pro Glu Lys Lys Pro Glu Pro Lys
Ala Glu Pro Lys Pro Glu 115 120 125 Lys Ala Gln Ser Lys Pro Ala Ala
Lys Ala Thr Glu Pro Ala Asn Thr 130 135 140 Glu Asp Asp Ala Val Ala
Ala Ala Ile Ala Ala Ala Thr Pro Ala Leu 145 150 155 160 Lys Asn
11166PRTAcinetobacter baumannii 11Met Thr Thr Glu Asn Lys Leu Asp
Glu Leu Lys Ala Asn Ala Ala Asp 1 5 10 15 Ala Lys Val Gln Gly Glu
Lys Ala Leu Asp Asp Leu Lys Glu Asn Val 20 25 30 Lys Glu Lys Gln
Thr Ala Gly Lys Glu Ala Ile Ala Asp Lys Val Asp 35 40 45 Glu Leu
Lys Thr Lys Ala Ala Asp Ala Lys Val Gln Gly Glu Lys Ala 50 55 60
Leu Glu Asp Leu Lys Glu Asn Val Lys Glu Lys Gln Ala Ala Ala Lys 65
70 75 80 Glu Ala Val Glu Asp Lys Ala Ser Asp Leu Lys Gly Lys Leu
Asp Asp 85 90 95 Ala Gln His Ser Leu Gln Asp Lys Phe Asp His Leu
Arg Thr Glu Ala 100 105 110 Ala His Lys Leu Asp Asp Ala Lys Ala Lys
Ala Ala Glu Leu Lys Glu 115 120 125 Glu Ala Ala Thr Lys Phe Asp Glu
Leu Lys Thr Gln Ala Thr Ala Lys 130 135 140 Phe Asp Glu Leu Lys Lys
Thr Ala Thr Glu Lys Leu Asn Lys Leu Lys 145 150 155 160 Asn His Asp
Ser Ala Glu 165 12230PRTAcinetobacter baumannii 12Met His Thr Arg
Arg Ile Leu Leu Ala Phe Ser Leu Ala Ala Ser Ala 1 5 10 15 Ala Ser
Val Ala Phe Ala Asp Tyr Gln Asn Ile Asn Gln Ser Thr Asp 20 25 30
Ser Asp Arg Leu Glu Gln Leu Ser Lys Thr Leu Ser Gln Gly Ser Tyr 35
40 45 Thr His Pro Asp Asp Leu Asp Leu Pro Ala Ser Ala Lys Val Ser
Val 50 55 60 Thr Leu Arg Glu Lys Thr Val Glu Leu Asn Asn Asp Ser
Leu Ala Lys 65 70 75 80 Lys Tyr Gly Thr Thr Thr Ala Lys Asn Ser Phe
Lys Thr Ser Ser Ser 85 90 95 Asn Pro Tyr Ser Trp Leu Val Ser His
Pro Leu Pro Asp Thr Val Arg 100 105 110 Val Ser Ser Asn Phe Gly Gly
Arg Thr Met Gly Gly Arg Ala Glu His 115 120 125 His Gly Gly Leu Asp
Met Ala Ala Pro Ser Gly Thr Pro Ile Tyr Ala 130 135 140 Thr Gly Pro
Gly Ile Val Thr Lys Ser Gly Trp Gly Thr Gly Tyr Gly 145 150 155 160
Gln Tyr Val Glu Ile Asn His Gly Asn Gly Tyr Leu Thr Arg Tyr Ala 165
170 175 His Ala Ser Arg Leu Met Val Arg Val Gly Asp Gln Val Ser Ala
Gly 180 185 190 Asp His Ile Ala Asn Val Gly Cys Thr Gly Arg Cys Thr
Gly Pro His 195 200 205 Leu His Tyr Glu Val Val Lys Asp Gly Gln Arg
Lys Asn Pro Ser Thr 210 215 220 Tyr Leu Ala Met Leu Pro 225 230
13238PRTAcinetobacter baumannii 13Met Gly Met Thr Phe Thr Asp Ile
Glu Asn Lys Ser Ala Lys Arg Leu 1 5 10 15 Ile Gly Ile Ala Ala Val
Ile Phe Leu His Leu Leu Val Ala Tyr Ile 20 25 30 Leu Met Ser Gly
Leu Ala Asn Asn Ile Gln Lys Pro Ala Glu Lys Pro 35 40 45 Val Glu
Leu Gln Ile Ile Gln Asp Ile Lys Pro Pro Pro Pro Pro Lys 50 55 60
Pro Glu Glu Pro Lys Pro Lys Glu Lys Pro Pro Glu Pro Pro Lys Met 65
70 75 80 Val Glu Lys Val Ala Lys Val Pro Glu Pro Pro Lys Glu Val
Glu Lys 85 90 95 Val Ala Thr Pro Val Gln Lys Thr Thr Pro Val Ala
Gln Thr Thr Lys 100 105 110 Val Ala Thr Pro Ala Pro Ala Ala Pro Ser
Thr Pro Ser Pro Ser Pro 115 120 125 Val Ala Ala Pro Ala Pro Val Ala
Ala Ala Ala Pro Ala Leu Lys Pro 130 135 140 Ala Gly Val Thr Arg Gly
Val Ser Glu Gly Ser Ala Gly Cys Glu Lys 145 150 155 160 Pro Glu Tyr
Pro Arg Glu Ala Leu Met Asn Glu Glu Gln Gly Thr Val 165 170 175 Arg
Ile Arg Val Leu Val Asp Thr Ser Gly Lys Val Ile Asp Ala Lys 180 185
190 Val Lys Lys Ser Ser Gly Ser Lys Thr Leu Asp Lys Ala Ala Thr Lys
195 200 205 Ala Tyr Ser Leu Cys Thr Phe Lys Pro Ala Met Lys Asp Gly
Val Pro 210 215 220 Gln Gln Asp Trp Tyr Glu Ile Glu Tyr Pro Phe Val
Ile Glu 225 230 235 14253PRTAcinetobacter baumannii 14Met Lys Met
Met Lys Thr Ala Ile Val Thr Ala Ser Val Leu Ala Ser 1 5 10 15 Ala
Ser Ile Phe Ala Gln Ser Ala Gly Val Asn Ala Gly Ala Ser Ala 20 25
30 Gln Val Asn Val Gln Pro Gly Gly Leu Val Ser Gly Val Ala Asn Thr
35 40 45 Val Lys Asn Thr Ala His Thr Val Gly Asn Thr Ala Lys His
Ala Gly 50 55 60 His Val Ala Ala Asp Thr Thr Val Lys Ala Thr Lys
Lys Thr Thr Gly 65 70 75 80 Lys Val Thr Glu Leu Ser Ser Lys Ala Ala
Thr Gly Thr Lys His Val 85 90 95 Ala Ser Glu Ala Val Thr Gly Thr
Lys His Phe Ala Thr Glu Ala Ala 100 105 110 Thr Gly Thr Lys Asn Leu
Ala Thr Lys Ala Ala Thr Gly Thr Lys Asn 115 120 125 Leu Ala Val Glu
Ala Lys Ala Asp Thr Lys Ala His Leu Asp Ala Val 130 135 140 Lys Thr
Lys Val Ala Glu Lys Gln Ala Asp Gln Lys Glu Phe Thr Ala 145 150 155
160 Glu Lys Gln Ala Asp Ala Gln Ala Arg Val Asp Ala Val Lys Ala Arg
165 170 175 Val Ala Gln Asn Gln Ala Glu Gln Lys Glu Phe Val Ala Asp
Thr Lys 180 185 190 Ala Asp Ala Gln Ala Lys Leu Asn Thr Ala Gln Pro
Ala His Gly Val 195 200 205 Asn Ala Gln Thr Gly Val Asn Val Gly Val
Asn Val Ala Gly Ile Asn 210 215 220 Ala Asn Ala Asn Val Asn Ala Gly
Ala Gln Ala Ser Thr Gln Lys Gly 225 230 235 240 Glu Lys Lys Ser Phe
Ile Lys Gly Leu Phe Gly Thr Asn 245 250 15294PRTAcinetobacter
baumannii 15Met Gln Met Lys Lys His Ser Leu Leu Phe Ile Ala Leu Met
Ser Thr 1 5 10 15 Thr Ser Leu Tyr Ala Asn Ile Pro Ile Glu Ser Arg
Gly Leu Ser Gln 20 25 30 Asn Asp Gly Ser Ala Ser Asn Thr Ser Ser
Ser Asn Ile Ser Val Pro 35 40 45 Thr Asn Leu Asn Trp Glu Leu Met
Gln Lys Asn Gln Gln Leu Glu Asn 50 55 60 Asp Ile Arg Thr Leu Arg
Gly Gln Leu Glu Glu Gln Ala Asn Asp Ile 65 70 75 80 Glu Gln Leu Lys
Lys Asp Leu Ala Asn Arg Tyr Thr Asp Leu Asp Gln 85 90 95 Arg Leu
Glu Leu Leu His Gln Lys Val Asp Pro Asp Ser Ala Thr Gln 100 105 110
Asp Asp Ser Ser Asn Ala Thr Ser Asp Asn Thr Thr Pro Ala Ser Ala 115
120 125 Pro Ala Pro Gln Thr Thr Glu Ser Asn Lys Val Ala Ala Val Pro
Ala 130 135 140 Thr Gln Thr Ser Glu Gln Gln Pro Ser Ala Pro Thr Thr
Thr Thr Gln 145 150 155 160 Pro Ala Pro Ala Ala Ala Gln Asn Gln Ser
Asn Ser Leu Glu Leu Glu 165 170 175 Lys Ala Ala Tyr Thr Val Ala Leu
Asp Ala Tyr Lys Gln Gly Gly Ala 180 185 190 Lys Lys Ala Ile Ala Pro
Met Gln Asn Phe Ile Lys Asn His Pro Asn 195 200 205 Ser Ile Tyr Thr
Gly Asn Ala Tyr Phe Trp Leu Ala Glu Phe His Leu 210 215 220 Ala Thr
Asp Pro Val Asn Tyr Asn Glu Ala Lys Lys Asn Tyr Asn Val 225 230 235
240 Val Ala Asn Gln Tyr Pro Asn Ser Ser Lys Ala Pro Arg Ala Leu Tyr
245 250 255 Gln Leu Tyr Ser Ile Ala Lys Asp Val Asp Lys Asn Thr Val
Ser Ala 260 265 270 Asn Gln Tyr Lys Asn Lys Leu Leu Ser Gln Tyr Pro
Lys Ser
Glu Glu 275 280 285 Ala Lys Phe Phe Asn Lys 290
16356PRTAcinetobacter baumannii 16Met Ser Met Asn Asn Lys Gln Arg
Trp Met Gly Gly Val Val Leu Leu 1 5 10 15 Gly Gly Gly Val Leu Leu
Ala Ala Leu Leu Leu Lys Gly Asn Glu Glu 20 25 30 Ile Lys Gln Val
Asp Val Gln Pro Gln Thr Ser Thr Ser Pro Lys Leu 35 40 45 Gln Ala
Lys Pro Lys Gln Ser Ala Gln Glu Gly Gln Met Val Gln Leu 50 55 60
Gln Pro Leu Ala Val Asp Val Glu Thr Glu Lys Arg Leu Leu Glu Glu 65
70 75 80 Gln Arg Arg Ser Arg Glu Lys Ala Val Ala Glu Gln Glu Ala
Arg Ala 85 90 95 Ala Glu Phe Leu Ala Met Gln Gln Gln Ala Glu Ala
Asp Ala Ala Arg 100 105 110 Lys Ala Ala Ala Glu Tyr Ala Ala Ile Asn
Ala Arg Arg Ala Ala Ala 115 120 125 Gln Glu Ser Ser Asp Asn Ile Pro
Pro Glu Val Ala Gly Ser Glu Asn 130 135 140 Lys Ala Lys Gly Gln Gln
Thr Asp Thr Lys Lys Ser Val Asp Leu Ala 145 150 155 160 Lys Ala Asp
Ala Asp Lys Lys Ala Ala Glu Ala Lys Arg Leu Ala Glu 165 170 175 Ala
Asp Lys Lys Ala Ala Glu Ala Lys Arg Gln Ala Glu Ala Asp Lys 180 185
190 Lys Ala Ala Glu Ala Lys Arg Gln Ala Glu Ala Asp Lys Lys Ala Ala
195 200 205 Glu Ala Lys Arg Gln Ala Glu Ala Asp Lys Lys Ala Ala Glu
Ala Lys 210 215 220 Arg Gln Ala Glu Ala Asp Lys Lys Ala Ala Glu Ala
Lys Arg Gln Ala 225 230 235 240 Glu Ala Asp Lys Lys Ala Ala Glu Ala
Lys Arg Lys Ala Glu Ala Glu 245 250 255 Lys Lys Ala Glu Ala Glu Lys
Ala Arg Glu Leu Leu Glu Asn Gly Asp 260 265 270 Lys Lys Trp Met Val
Gln Val Ala Leu Ala Ala Asn Gln Ala Asn Ala 275 280 285 Asp Ala Val
Val Ser Lys Leu Arg Ala Lys Gly Tyr Lys Val Thr Thr 290 295 300 Ser
Pro Thr Ser Lys Gly Ile Arg Ile Met Val Gly Pro Ala Lys Asp 305 310
315 320 Arg Asp Thr Ala Asp Thr Thr Arg Lys Lys Ile Thr Ser Asp Ala
Ser 325 330 335 Leu Asn Met Lys Ser Ala Trp Val Ile Asp Trp Val Pro
Leu Asp Gln 340 345 350 Arg Lys Ser Asp 355 17367PRTAcinetobacter
baumannii 17Met Ala Asn Thr Arg Tyr Glu Asp Asp Asn Asn Ser Ser Gly
Thr Ser 1 5 10 15 Asn Arg Gly Phe Ala Ser Met Asp Pro Glu Arg Val
Arg Glu Ile Ala 20 25 30 Ser Lys Gly Gly Arg Ala Ala His Ala Ser
Gly Asn Ala His Glu Phe 35 40 45 Thr Ser Glu Glu Ala Arg Glu Ala
Gly Arg Ala Ala His Ala Ser Gly 50 55 60 Asn Ala His Glu Phe Thr
Ser Glu Glu Ala Arg Glu Ala Gly Ala Leu 65 70 75 80 Ser His Lys Asn
Asp Asp Arg Asn Gly Arg Gly Arg Ser Arg Tyr Asp 85 90 95 Asp Asp
Glu Asp Asp Asp Arg Gly Arg Ser Ser Gly Arg Gly Arg Gly 100 105 110
Arg Ser Arg Tyr Asp Asp Asp Asp Glu Asp Asp Asp Arg Gly Arg Ser 115
120 125 Gly Gly Arg Gly Arg Gly Arg Gly Arg Asp Asp Asp Asp Glu Asp
Asp 130 135 140 Asp Arg Gly Arg Ser Gly Gly Arg Gly Arg Gly Arg Ser
Arg Asp Asp 145 150 155 160 Asp Asp Glu Asp Asp Asp Arg Gly Arg Ser
Gly Gly Arg Gly Arg Gly 165 170 175 Arg Ser Arg Arg Asp Asp Asp Asp
Glu Asp Asp Asp Arg Gly Arg Ser 180 185 190 Gly Gly Arg Gly Arg Gly
Arg Ser Arg Arg Asp Asp Asp Asp Glu Asp 195 200 205 Asp Asp Arg Gly
Arg Ser Gly Gly Arg Gly Arg Gly Arg Ser Arg Tyr 210 215 220 Asp Asp
Asp Asp Glu Asp Asp Asp Arg Gly Arg Ser Gly Gly Arg Gly 225 230 235
240 Arg Gly Arg Ser Arg Arg Asp Asp Asp Asp Glu Asp Asp Asp Arg Gly
245 250 255 Arg Ser Gly Gly Arg Gly Arg Gly Arg Ser Arg Tyr Asp Asp
Asp Asp 260 265 270 Glu Asp Asp Asp Arg Gly Arg Ser Gly Gly Arg Gly
Arg Gly Arg Ser 275 280 285 Arg Arg Asp Asp Asp Asp Glu Asp Asp Asp
Arg Gly Arg Ser Gly Gly 290 295 300 Arg Gly Arg Gly Arg Ser Arg Tyr
Asp Asp Asp Asp Glu Asp Asp Asp 305 310 315 320 Arg Gly Arg Ser Gly
Gly Arg Gly Arg Gly Arg Ser Arg Arg Asp Asp 325 330 335 Asp Asp Asp
Asp Asp Asp Arg Arg Gly Arg Ser Asp Gly Arg Gly Gln 340 345 350 Asn
Ser Arg Asn Gln Lys Arg Asp Ala Tyr Gly Arg Phe Thr Ser 355 360 365
18420PRTAcinetobacter baumannii 18Met Leu Tyr Val Ile Pro Phe Ile
Ile Leu Leu Val Val Ala Val Ile 1 5 10 15 Leu Lys Lys Arg Glu Asn
Ser Gln Lys Gln Glu Ala Thr Ser Pro Lys 20 25 30 Asn Ile Asn Arg
Lys Ser Gly Lys Lys Ala Ser Ala Lys Ser Ser Lys 35 40 45 Ser Ser
Arg Glu Lys Ile Lys Ala Lys Val Ile Glu Glu Asn Ile Pro 50 55 60
Ala Ile Pro Gln Ser Asn Pro Val Pro Glu Ala Leu Arg His Asn Ile 65
70 75 80 Gln Gln Leu Ile Gln Glu Lys Gln Phe Ser Ala Ala Glu Ala
Gln Val 85 90 95 Asn Gln Ala Leu Lys Lys Asp Asn Thr Gln His Glu
Leu Tyr Leu Leu 100 105 110 Leu Leu Glu Ile His Ile Ala Gln Lys Asp
Glu Phe Ala Ile Gln Gln 115 120 125 Leu Ile Ser His Ile Arg Ser Leu
Gly Leu Asn Glu Ile Ala Ala Gln 130 135 140 Ala Glu Thr Arg Gln Lys
Glu Tyr Glu Ser Ser Ser Gln Pro Asp Ala 145 150 155 160 Ile Asp Phe
Pro Gln Ala Gln Thr Tyr Glu Glu Pro Lys Asn Thr Asp 165 170 175 Thr
Thr Ala Gln Phe Asp Glu Leu Thr Thr Ser Ser Ser Glu Ala Ser 180 185
190 Phe Asp Asp Leu Gln Lys Asp Tyr Thr Pro Val Lys Gln Glu Pro Ala
195 200 205 Ile Glu Ile Glu Pro Leu Glu Phe Asn Phe Ser Phe Glu Gln
Asn Ser 210 215 220 Ala Thr Glu Asn Thr Asn Gln Pro Ala Gln Gln Pro
Glu Leu Ser Ser 225 230 235 240 Thr Gln Glu Thr Asn Glu Leu Ala Asp
Leu Glu Phe Ser Phe Asp Leu 245 250 255 Ala Pro Leu His Glu Thr Glu
Glu Lys Ser Gln Ala Val Glu Val Lys 260 265 270 Ala Asp Gln Glu Asn
Ser Ile Asn Ala Leu Asp Phe Asn Phe Asp Leu 275 280 285 Asn Pro Ser
Ser Ser Glu Thr Lys Ser Val Gln Gln Ala Pro Ser Leu 290 295 300 Asp
Glu Ile Lys Leu Ile Glu Gln Ala Pro Leu Glu Ala Thr Ser Ile 305 310
315 320 Ala Pro Leu Glu Phe Ser Leu Asp Glu Pro Ala Leu Val Pro Ala
Pro 325 330 335 Glu Leu Glu Thr Gln Asn His Ile Asp Val Val Asn Glu
Ala Ala Thr 340 345 350 Gln Thr Gln Ile Glu Asp Pro Leu Leu Glu Ala
Phe Pro Glu Leu Lys 355 360 365 Gln Ile Asn Glu Asn Glu Leu Asp Leu
Lys Leu Ala Glu Gln Tyr Ile 370 375 380 Lys Phe Gly Ala Asn Gln Ala
Ala Arg Asn Leu Leu Gln Gly Asp Glu 385 390 395 400 Gln Lys Phe Asn
Thr Glu Gln Gln Gln His Ala Lys Asn Leu Leu Asn 405 410 415 Arg Ile
Ala Ser 420 19445PRTAcinetobacter baumannii 19Met Pro Lys Ile Lys
Pro Ile Lys Leu Val Ile Ile Val Val Cys Ile 1 5 10 15 Ala Ile Ile
Ala Val Leu Ala Trp Lys Phe Leu Lys Pro Lys Gln Gln 20 25 30 Gln
Pro Gln Tyr Ile Thr Ala Glu Val Thr Arg Gly Asp Ile Glu Asn 35 40
45 Asn Val Leu Ala Thr Gly Thr Leu Asp Ala Thr Lys Leu Ile Ser Val
50 55 60 Gly Ala Gln Val Ser Gly Gln Val Lys Lys Met Tyr Val Gln
Leu Gly 65 70 75 80 Asp Gln Val Lys Gln Gly Gln Leu Ile Ala Gln Ile
Asp Ser Thr Thr 85 90 95 Gln Glu Asn Ser Leu Lys Thr Ser Asp Ala
Asn Ile Lys Asn Leu Glu 100 105 110 Ala Gln Arg Leu Gln Gln Ile Ala
Ser Leu Asn Glu Lys Gln Leu Glu 115 120 125 Tyr Arg Arg Gln Gln Gln
Met Tyr Ala Gln Asp Ala Thr Pro Arg Ala 130 135 140 Asp Leu Glu Ser
Ala Glu Ala Ala Tyr Lys Thr Ala Gln Ala Gln Val 145 150 155 160 Lys
Ala Leu Asp Ala Gln Ile Glu Ser Ala Lys Ile Thr Arg Ser Thr 165 170
175 Ala Gln Thr Asn Ile Gly Tyr Thr Arg Ile Val Ala Pro Thr Asp Gly
180 185 190 Thr Val Val Ala Ile Val Thr Glu Glu Gly Gln Thr Val Asn
Ala Asn 195 200 205 Gln Ser Ala Pro Thr Ile Val Lys Ile Ala Lys Leu
Gln Asn Met Thr 210 215 220 Ile Lys Ala Gln Val Ser Glu Ala Asp Ile
Met Lys Val Glu Lys Gly 225 230 235 240 Gln Gln Val Tyr Phe Thr Thr
Leu Gly Asp Glu Thr Lys Arg Tyr Ala 245 250 255 Thr Leu Arg Gln Ile
Glu Pro Ala Pro Asp Ser Ile Ser Ser Glu Ser 260 265 270 Asn Ser Thr
Thr Ser Ser Thr Thr Ser Ser Ala Val Tyr Tyr Asn Ala 275 280 285 Leu
Phe Asp Val Pro Asn Thr Asp Gly Lys Leu Arg Ile Asp Met Thr 290 295
300 Ala Gln Val Tyr Ile Val Leu Asn Ser Ala Lys Asn Ala Leu Leu Val
305 310 315 320 Pro Ser Ser Ala Leu Ser Ser Lys Gln Phe Ser Gly Gln
Arg Lys Gln 325 330 335 Gly Gln Ser Ala Asp Lys Ala Ser Ser Thr Pro
Ser Ala Glu Arg Lys 340 345 350 His Gln Gly Asn Gly Val Arg Leu Glu
Arg Leu Asn Leu Thr Pro Glu 355 360 365 Gln Lys Gln Leu Ile Glu Gln
Gly Lys Ala Thr Leu Ser Val Val Arg 370 375 380 Val Leu Gln Ala Asp
Gly Thr Thr Lys Pro Thr Gln Ile Leu Val Gly 385 390 395 400 Ile Asn
Asn Arg Val Asn Ala Gln Val Leu Ala Gly Leu Lys Gln Gly 405 410 415
Asp Gln Val Val Ile Ala Asp Ser Ser Glu Asn Ser Ala Ala Ser Ala 420
425 430 Asn Ser Gly Asn Asn Arg Arg Arg Gly Pro Met Gly Met 435 440
445 20711PRTAcinetobacter baumannii 20Met Asn Ile Pro Pro Arg Pro
Phe Lys Leu Ser Val Ile Ala Cys Ala 1 5 10 15 Ile Cys Tyr Ala Asn
Leu Thr Tyr Ala Gln Asp Ala Gln Val Gln Ala 20 25 30 Leu Gln Thr
Ile Gln Val Lys Ala Ser Asn Ala Glu Gln Ser Ser Glu 35 40 45 Gln
Thr Lys Ala Tyr Asn Val Lys Asn Ser Ser Ser Ala Thr Lys Leu 50 55
60 Asn Ile Glu Ala Lys Glu Thr Pro Gln Thr Ile Asn Val Val Thr Arg
65 70 75 80 Gln Gln Ile Glu Asp Phe Gly Leu Thr Ser Thr Arg Asp Val
Leu Arg 85 90 95 Asn Thr Pro Gly Val Thr Val Ser Asn Gln Glu Thr
Glu Arg Thr Thr 100 105 110 Tyr Met Ala Arg Gly Phe Glu Ile Ser Asn
Ile Leu Thr Asp Gly Val 115 120 125 Gly Phe Pro Leu Ser Gly Tyr Asn
Tyr Asn Asn Thr Asn Pro Asp Thr 130 135 140 Tyr Phe Tyr Asp Arg Val
Glu Val Val Lys Gly Ala Asp Ser Leu Thr 145 150 155 160 Asn Ala Phe
Gly Asp Pro Ser Ala Thr Ile Asn Asn Ile Arg Lys Arg 165 170 175 Pro
Thr Gln Glu Phe Gln Ala Ser Gly Gly Val Ser Tyr Gly Ser Trp 180 185
190 Asp Thr Gln Arg Tyr Glu Ala Asp Val Ser Gly Ser Ile Leu Pro Ser
195 200 205 Gly Lys Val Arg Gly Arg Ile Met Gly Tyr Glu Gln Thr Gly
Asp Ser 210 215 220 Tyr Leu Asp Arg Tyr Ser Ala Glu Lys Asn Gly Phe
Ala Gly Ile Val 225 230 235 240 Glu Ala Asp Leu Thr Asp Ser Thr Leu
Leu Thr Ala Gly Tyr Ser Gln 245 250 255 Glu Gln Asn Lys Pro Asn Ala
Asn Asn Trp Gly Ala Leu Pro Leu Leu 260 265 270 Asp Ala Asn Gly Lys
Gln Ile Ser Tyr Asp Arg Ser Tyr Asn Pro Asn 275 280 285 Pro Asp Trp
Ala His Trp Asp Asn Glu Thr Gln Asn Ala Phe Val Glu 290 295 300 Leu
Lys Gln Lys Leu Asn Asp Gln Trp Asn Ala Lys Leu Thr Tyr Asn 305 310
315 320 Tyr Leu Asp Thr Lys His Asn Ser Arg Leu Leu Tyr Tyr Tyr Gly
Tyr 325 330 335 Pro Lys Ala Asp Gly Ser Gly Val Ser Leu Thr Pro Trp
Gly Gly Gln 340 345 350 Glu His Gln Glu Lys His Ala Val Asp Phe Asn
Leu Glu Gly Thr Tyr 355 360 365 Lys Leu Phe Asn Arg Glu His Glu Ala
Thr Leu Gly Tyr Ser Tyr Val 370 375 380 Arg Asn His Gln Gln Asp Lys
Gln Ser Thr Gly Thr Ile Asn Asp Ser 385 390 395 400 Asn Val Ile Lys
Ser Thr Thr Thr Asp Trp Ala Ser Trp Thr Pro Gln 405 410 415 Ser Ile
Thr Trp Ser Asp Phe Thr Glu Ala Ala Asn Tyr Lys Gln Asn 420 425 430
Ile Asn Ser Ile Tyr Ala Ala Thr Arg Leu His Leu Asn Glu Asp Leu 435
440 445 Lys Leu Leu Leu Gly Ala Asn Tyr Val Gln Ala Glu Ser Lys Gly
Glu 450 455 460 Ser Tyr Ser Ser Pro Met Ser Tyr Ser Glu Ser Lys Val
Ser Pro Tyr 465 470 475 480 Val Gly Leu Thr Tyr Asn Phe Thr Pro Glu
Tyr Thr Gly Tyr Met Ser 485 490 495 Tyr Thr Ser Ile Phe Arg Pro Gln
Thr Gly Ile Asp Lys Asp Thr Asn 500 505 510 Gln Ala Leu Lys Pro Ile
Glu Gly Lys Ser Tyr Glu Met Gly Val Lys 515 520 525 Ser Ser Trp Leu
Asp Asp Arg Leu Thr Gly Thr Leu Ser Val Phe Lys 530 535 540 Thr Glu
Gln Asn Asn Tyr Pro Leu Arg Asn Ser Asp Gly Asn Pro Leu 545 550 555
560 Asn Arg Lys Val Pro Thr Ser Asp Leu Glu Ser Gln Gly Val Glu Val
565 570 575 Gly Leu Ser Gly Gln Ile Thr Asp Asn Val Asn Leu Ser Phe
Gly Tyr 580 585 590 Ala Gln Phe Ser Ile Lys Asp Thr Lys Asn Gly Gly
Glu Ala Arg Thr 595 600 605 Tyr Asn Pro Asn Gln Thr Leu Asn Leu Leu
Thr Thr Tyr Thr Pro Pro 610 615 620 Val Leu Pro Lys Leu Lys Val Gly
Ala Gly Leu Gln Trp Gln Asp Gly 625 630 635 640 Ile Lys Leu Tyr Asp
Ser Asn Val Asn Gly Thr Ile Lys Gln Asp Ala 645 650 655 Tyr Ala Leu
Val Asn Leu Met Ala Ser Tyr Glu Val Asn Asp His Ile 660 665 670 Thr
Leu Gln Ala Asn Gly Asn Asn Ile Phe Asp Lys Lys
Tyr Leu Asn 675 680 685 Ser Phe Pro Asp Gly Gln Ala Phe Tyr Gly Ala
Pro Ala Asn Tyr Thr 690 695 700 Val Ala Val Lys Phe Lys Tyr 705 710
21727PRTAcinetobacter baumannii 21Met Lys Leu Gln Thr Ile Ala Cys
Ala Val Ala Ile Ala Thr Gly Gly 1 5 10 15 Leu Phe Phe Ser His Thr
Met Asn Glu Ala Arg Ala Ala Thr Asn Thr 20 25 30 Ala Ala Val Ser
Gln Ser Ile Gln Pro Thr Gln Glu Gln Ala Leu Val 35 40 45 Ala Arg
Gln Leu Ala Thr Leu Val Asp Arg Gln His Tyr Leu Asn Met 50 55 60
Arg Leu Asp Ala Asn Thr Ser Asn Arg Ile Leu Asp Met Tyr Leu Asp 65
70 75 80 Ser Leu Asp Pro Asp His Ser Leu Phe Leu Asp Ala Glu Val
Gln Asn 85 90 95 Tyr Lys Lys Leu Tyr Gly Ser Asn Phe Gly Ala Ser
Leu Lys Ala Gly 100 105 110 Asn Leu Thr Gly Pro Phe Ala Ile His Gln
Gln Tyr Arg Glu Arg Leu 115 120 125 Lys Gln Phe Tyr Glu Phe Met Leu
Ala Glu Leu Lys Lys Pro Gln Asn 130 135 140 Leu Lys Gln Pro Asn Thr
Phe Ile Glu Val Asp Arg Glu Lys Ala Pro 145 150 155 160 Tyr Phe Lys
Thr Ser Ala Glu Gln Gln Asn His Trp Arg Lys Met Leu 165 170 175 Val
Ser Gln Leu Ile Asn Leu Thr Ile Ser Arg Glu Glu Glu Gln Ala 180 185
190 Lys Gln Lys Ala Leu Lys Glu Asn Pro Ser Leu Ala Asp Gly Gln Asp
195 200 205 Leu Thr Gly Pro Glu Asp Leu Thr Pro Ala Gln Thr Leu Thr
Lys Arg 210 215 220 Tyr Thr Arg Gln Leu Glu Arg Ile Ser Arg Val Lys
Ser Asp Asp Val 225 230 235 240 Leu Asp Lys Thr Leu Asn Ala Met Leu
Ala Thr Tyr Asp Pro His Ser 245 250 255 Asn Tyr Tyr Pro Pro Ile Asp
Ala Ile Glu Leu Asn Arg Gln Thr Thr 260 265 270 Leu Gln Leu Glu Gly
Ile Gly Val Ser Ile Arg Pro Glu Arg Gly Asn 275 280 285 Glu Asp Tyr
Thr Lys Ile Glu Thr Ile Val Glu Gly Gly Pro Ala Ser 290 295 300 Lys
Ser Gly Gln Val Lys Ser Gly Asp Arg Ile Val Gly Val Ala Gln 305 310
315 320 Glu Gly Gly Lys Met Ile Asp Val Val Gly Trp Ser Ser Ser Glu
Ile 325 330 335 Val Gly Leu Ile Arg Gly Lys Arg Gly Thr Lys Val Thr
Leu Lys Leu 340 345 350 Leu Gly Ala Gly Ala Ser Met Ser Gln Ala Arg
Asn Val Thr Leu Val 355 360 365 Arg Asp Val Ile Gln Glu Glu Asp Ala
Gly Val Arg Ser Arg Thr Val 370 375 380 Glu Val Thr Arg Asp Gly Lys
Lys His Leu Leu Gly Val Ile Glu Ile 385 390 395 400 Pro Ser Phe Tyr
Phe Asp Tyr Arg Ser Arg Arg Ala Gly Gln Gln Tyr 405 410 415 Arg Ser
Val Ser Glu Asp Thr Ala Asn Ala Phe Glu Ala Leu Lys Ala 420 425 430
Lys Lys Val Glu Gly Ile Ile Ile Asp Leu Arg Asn Asp Pro Gly Gly 435
440 445 Ser Leu Glu Glu Val Ala Arg Met Leu Gly Gln Val Ile Lys Ser
Gly 450 455 460 Pro Val Val Gln Ile Arg Asp Gly Asn Gly Asn Val Ser
Val Phe Glu 465 470 475 480 Asp Asn Asp Gly Gly Gln Gln Ile Tyr Thr
Gly Pro Leu Ala Val Leu 485 490 495 Val Asn Leu Ala Ser Ala Ser Ala
Ser Glu Ile Tyr Ser Ala Ala Ile 500 505 510 Gln Asp Tyr Glu Arg Gly
Ile Ile Ile Gly Ser Thr Thr Thr Gly Lys 515 520 525 Gly Thr Ala Gln
Val Gln Leu Asp Thr Leu Ala Tyr Gly Gln Ala Thr 530 535 540 Leu Thr
Gln Arg Lys Phe Tyr Arg Val Thr Gly Gly Ser Thr Gln Asn 545 550 555
560 Lys Gly Val Val Pro Asp Ile Lys Leu Val Asp Ile Tyr Asn Glu Glu
565 570 575 Phe Gly Glu Arg Lys Ser Lys Asn Ala Leu Lys Trp Asp Thr
Ile Pro 580 585 590 Thr Ala Pro Phe Lys Arg Glu Gly Ser Val Gln Pro
Tyr Val Ala Lys 595 600 605 Leu Ser Gln Leu Ser Glu Gln Arg Val Ala
Val Asp Pro Gln Phe Lys 610 615 620 Tyr Leu Asn Lys Arg Thr Ala Ile
Ala Lys Val Thr Ser Asp Gln Lys 625 630 635 640 Gln Val Val Leu Asp
Ile Asp Lys Arg Arg Ala Glu Leu Leu Ser Leu 645 650 655 Glu Lys Gln
Thr Leu Asp Ala Glu Asn Glu Arg Arg Ile Ala Thr Gly 660 665 670 Gln
Lys Pro Phe Pro Asn Trp Glu Ser Tyr Gln Ala Ser Leu Asp Ala 675 680
685 Leu Ala Glu Ser Arg Ala Lys Met Lys Ala Asn Gln Arg Pro Ala Leu
690 695 700 Pro Glu Glu Glu Thr Phe Val Asn Glu Ala Ala Asn Val Leu
Met Asp 705 710 715 720 Tyr Ala Lys Leu Gln Asn Arg 725
22728PRTAcinetobacter baumannii 22Met Thr Arg Ile Ile Val Ala Ser
Lys Glu Gly Leu Asp Val Leu Gln 1 5 10 15 Asp Gly Gln Leu Asn Lys
Val Val Leu Asn Gln Pro Thr Ile Ile Gln 20 25 30 Ile Gly Val Ser
Gln Lys Asp Ile Ala Ser Met Glu Lys Gln Gly Gly 35 40 45 Ser Leu
Val Ile His Leu Lys Asn Gly Glu Thr Ile Val Leu Glu Asn 50 55 60
Phe Phe Asn Glu Ala Thr Asn Thr Thr Glu His Ser Leu Val Phe Pro 65
70 75 80 Thr Glu Gln Gly Lys Phe Val Glu Ala Gln Phe Asp Ala Gln
Gly Lys 85 90 95 Val Ile Asp Tyr Arg Gly Leu Asn His Val Thr Asp
Leu Ala Tyr Thr 100 105 110 Ser Thr Ser Pro Ser Ala Ala Thr Met Ala
Val Asp Asn Asp Pro Ser 115 120 125 Phe Ser Met Gly Asn Val Leu Lys
Ala Gly Leu Ala Val Leu Ala Ala 130 135 140 Glu Gly Leu Tyr Leu Trp
Ala Phe Asp Lys Asp Asp Lys Asp Asp Ser 145 150 155 160 Pro Ser Thr
Pro Asp Leu Ile Ala Pro Ala Ala Pro Thr Ala Thr Leu 165 170 175 Ala
Asp Asp Thr Val Thr Val Thr Gly Lys Thr Glu Ala Asn Ala Lys 180 185
190 Ile Tyr Ile Lys Asp Ala Ala Gly Asn Thr Val Ala Ser Gly Val Ala
195 200 205 Asp Ala Ser Gly Asn Tyr Thr Ile Lys Leu Asp Lys Pro Leu
Val Asn 210 215 220 Gly Asp Lys Leu Asn Val Ile Ala Gln Asp Ala Ala
Gly Asn Asn Ser 225 230 235 240 Lys Val Thr Val Val Thr Gly Thr Lys
Asp Thr Ile Ala Pro Asp Val 245 250 255 Pro Gln Ala Gln Leu Ser Asp
Asp Gly Ser Leu Leu Thr Gly Lys Ala 260 265 270 Glu Ala Asn Ala Lys
Ile Thr Val Tyr Asp Ala Thr Gly Lys Val Leu 275 280 285 Gly Thr Val
Phe Ala Asn Lys Asp Gly Ile Tyr Ser Leu Lys Leu Thr 290 295 300 Pro
Pro Leu Thr Ser Glu Ala Gly Gly Lys Val Val Ala Glu Asp Ala 305 310
315 320 Ala Gly Asn Lys Ser Glu Glu Val Lys Ile Ile Ala Gly Lys Asp
Thr 325 330 335 Ile Pro Pro Ala Ser Pro Phe Val Glu Val Asn Lys Glu
Gly Ser Val 340 345 350 Ile His Gly Lys Thr Glu Ala Asn Ala Lys Val
Gln Ile Lys Asp Ala 355 360 365 Asp Gly Lys Val Ile Gly Ser Gly Thr
Ala Asp Ala Gln Gly Glu Phe 370 375 380 Gln Ile Thr Leu Ser Pro Ala
Leu Lys Glu Ala Gln Lys Gly Thr Val 385 390 395 400 Val Val Glu Asp
Ala Ala Gly Asn Val Ser Lys Pro Val Glu Ile Thr 405 410 415 Pro Gly
Phe Asp Ser Ile Ala Pro Asp Lys Pro Thr Val Gln Ile Asn 420 425 430
Thr Asp Gly Thr Ser Val Thr Gly Thr Ala Glu Ala Asn Ala Lys Ile 435
440 445 Glu Ile Lys Asp Thr Thr Gly Lys Val Ile Gly Ser Gly Thr Ala
Asp 450 455 460 Ala Asn Gly Lys Phe Thr Ile Ser Ile Ser Pro Ala Leu
Thr Asp Asn 465 470 475 480 Lys His Ala Ser Val Ser Ala Ile Asp Asn
Ala Gly Asn Lys Ser Glu 485 490 495 Val Val Asp Ile Val Gly Thr Lys
Asp Thr Thr Pro Pro Ala Lys Pro 500 505 510 Ile Leu Asn Ser Val Asp
Asp Asp Val Gly Ala Val Lys Gly Ala Ile 515 520 525 Thr Ala Gly Ser
Glu Thr Asp Asp Ala Arg Pro Lys Leu Thr Gly Ser 530 535 540 Gly Glu
Ala Asn Ala Thr Leu Thr Ile Tyr Asp Asn Gly Val Ala Ile 545 550 555
560 Gly Val Val Thr Val Thr Ser Gly Arg Ser Trp Ser Phe Thr Phe Asp
565 570 575 Lys Asp Leu Ala Leu Gly Lys His Thr Ile Thr Leu Thr Gln
Thr Asp 580 585 590 Ala Ala Gly Leu Thr Ser Glu Ala Ser Ser Pro Phe
Thr Phe Tyr Val 595 600 605 Val Ala Pro Lys Ala Ala Ser Leu Ser Glu
Thr Ser Val Asp Ile Leu 610 615 620 Ser Thr Glu Gly Pro Ser Leu Ala
Asp Ser Val Gly Leu His Thr Leu 625 630 635 640 Lys Val Ala Gln Asn
Thr Thr Thr Glu Thr Asn Asn Pro Gln Lys Ser 645 650 655 Val Pro Leu
Asp Asp Leu Leu Lys Ser Ser Thr Ala Ser Glu Ser Asp 660 665 670 Pro
Ile Ala Lys Leu Leu Ser Ser Thr Ala Leu Lys Thr Thr Gln Ala 675 680
685 Ser Glu Pro Ile Glu Val Asn Ala Ser Val Gly Gln Thr Thr Ser Asn
690 695 700 Pro Asn His Pro Leu Pro Asp Thr Thr Ser Ser Val Leu Gln
Asn Leu 705 710 715 720 Leu Asp Gln Thr Tyr Pro Val Val 725
23754PRTAcinetobacter baumannii 23Met Ser Lys Arg Ile Ile Gln Ser
Val Leu Ser Val Ser Val Leu Ala 1 5 10 15 Ser Met Met Ser Met Ala
Phe Ala Ala Gln Asn Glu Gln Glu Gln Ala 20 25 30 Glu Gln Thr Leu
Glu Lys Pro Ala Glu Pro Val Lys Leu Glu Thr Ile 35 40 45 Phe Val
Thr Ala Glu Glu Gln Val Lys Gln Ser Leu Gly Val Ser Val 50 55 60
Ile Thr Lys Glu Asp Leu Glu Lys Leu Pro Val Arg Asn Asp Ile Ser 65
70 75 80 Asp Tyr Val Arg Arg Met Pro Gly Val Asn Leu Thr Gly Asn
Ser Ala 85 90 95 Thr Gly Gln Arg Gly Asn Asn Arg Gln Ile Asp Ile
Arg Gly Met Gly 100 105 110 Pro Glu Asn Thr Leu Ile Leu Val Asp Gly
Lys Pro Ile Asn Ser Arg 115 120 125 Asn Ser Val Arg Tyr Gly Trp Lys
Gly Glu Arg Asp Thr Arg Gly Asp 130 135 140 Ser Asn Trp Val Pro Ala
Glu Ala Ile Glu Ser Ile Glu Val Leu Arg 145 150 155 160 Gly Pro Ala
Ala Ala Arg Tyr Gly Ser Gly Ala Ala Gly Gly Val Val 165 170 175 Asn
Ile Ile Thr Lys Lys Val Thr Asn Glu Thr His Gly Ser Val Glu 180 185
190 Phe Tyr Thr Ser Gln Pro Glu Asp Ser Lys Glu Gly Ser Ser Asn Arg
195 200 205 Val Gly Phe Asn Val Ser Gly Pro Leu Ile Lys Asp Val Leu
Ser Tyr 210 215 220 Arg Leu Tyr Gly Asn Tyr Asn Lys Thr Glu Ala Asp
Asp Val Asp Ile 225 230 235 240 Asn Lys Ser Ile Gly Ser Thr Ala Ala
Gly Arg Glu Gly Val Lys Asn 245 250 255 Lys Asp Ile Ser Gly Arg Leu
Ala Trp Gln Ala Thr Asp Gln Gln Thr 260 265 270 Val Leu Leu Asp Ile
Ser Ser Ser Lys Gln Gly Asn Ile Tyr Ser Gly 275 280 285 Asp Ser Gln
Leu Asn Ala Asn Ala Glu Ala Asp Ala Ile Leu Ser Gln 290 295 300 Leu
Ile Gly Lys Glu Thr Asn Thr Met Tyr Arg Asp Ser Tyr Ala Leu 305 310
315 320 Thr His Glu Gly Asp Trp Ser Trp Gly Lys Ser Lys Leu Val Ala
Gln 325 330 335 Tyr Asp Lys Thr His Asn Lys Arg Leu Pro Glu Gly Leu
Ala Gly Ser 340 345 350 Val Glu Gly Lys Ile Asn Asn Leu Asp Asp Lys
Ala Thr Ser Arg Leu 355 360 365 Glu Thr Leu Arg Phe Asn Gly Glu Ala
Asn Ile Pro Phe Glu Tyr Tyr 370 375 380 Leu Pro Gln Val Leu Thr Val
Gly Thr Glu Trp Val Glu Asp Arg Phe 385 390 395 400 Lys Asp Asn Val
Ser Thr Thr Gln Gly Lys Asp Ser Ser Gly Ser Gly 405 410 415 Tyr Gly
Asp Gln Leu Ala Lys Gly Asp Arg Ser Lys Met Glu Ser Arg 420 425 430
Ile Ala Ser Ala Tyr Ile Glu Asp Asn Leu Lys Val Thr Asp Ser Thr 435
440 445 Asp Val Val Leu Gly Leu Arg Phe Asp Asp His Ser Lys Ser Gly
Ser 450 455 460 Asn Trp Ser Pro Ser Leu Asn Ile Thr Gln Lys Leu Asn
Asp Asn Phe 465 470 475 480 Thr Leu Lys Gly Gly Val Ala Lys Ala Tyr
Lys Ala Pro Asn Met Tyr 485 490 495 Gln Asn Ala Glu Gly Tyr Leu Leu
Ser Thr Asn Gly Asn Gly Cys Pro 500 505 510 Ala Asn Ile Glu Ser Arg
Cys Leu Leu Gln Gly Asn Gly Asp Leu Lys 515 520 525 Pro Glu Thr Ser
Val Asn Lys Glu Leu Gly Ile Gln Phe Gln Arg Asp 530 535 540 Ile Val
Asn Ala Ser Leu Thr Trp Phe Arg Asn Asp Tyr Lys Asp Lys 545 550 555
560 Ile Val Ala Gly Thr His Val Val Gly Thr Val Asp Gly Ser Ser Thr
565 570 575 Asn Ala Asn Thr Gly Ala Val Thr Asn Thr Lys Trp Asn Ile
Leu Arg 580 585 590 Trp Glu Asn Thr Pro Lys Ala Leu Ile Gln Gly Phe
Glu Gly Ser Leu 595 600 605 Gly Leu Asp Phe Gly Asp Ile Arg Trp Thr
Asn Asn Phe Thr Tyr Met 610 615 620 Met Asp Ser Lys Asp Lys Gln Thr
Gly Asn Pro Leu Ser Leu Val Pro 625 630 635 640 Ile Tyr Thr Ile Asn
Ser Ile Phe Asp Tyr Asp Ile Thr Asp Gln Leu 645 650 655 Asp Val Asn
Phe Val Phe Thr Gln Tyr Gly Arg Gln Lys Ser Arg Gln 660 665 670 Phe
Ala Glu Asn Arg Leu Glu Ser Gly Ile Gly Ser Gly Gly Ala Asn 675 680
685 Ser Ala Leu Lys Pro Ser Thr Val Lys Ser Tyr Ser Thr Ala Gly Ile
690 695 700 Asn Val Gly Tyr Lys Phe Ser Asp Gln Ile Ser Thr Arg Val
Gly Val 705 710 715 720 Ser Asn Leu Phe Asp Lys Gln Ile Leu Arg Asp
Ser Asn Ser Ile Ser 725 730 735 Gln Thr Tyr Asn Glu Pro Gly Arg Ala
Tyr Tyr Ala Ser Leu Lys Tyr 740 745 750 Ser Phe
24906PRTAcinetobacter baumannii 24Met Pro Ser Lys Ile Lys Phe Lys
Gln Ser Thr Leu Ser His Ser Met 1 5 10 15 His Leu Ile Leu Lys Met
Gln Ser Ile Pro Lys Leu Ile Cys Ser Ser 20 25 30 Leu Leu Leu Ser
Leu Cys Val Thr Pro Cys Tyr Ala Gln Ser Ser Ala 35 40 45 Glu
Thr Val Ile Pro Glu Ala Asn Gln Thr Val Thr Asp Ser Leu Val 50 55
60 Gln Gln Thr Asn Thr Asn Asn Pro Ser Asp Val Pro Ile Thr Asp Val
65 70 75 80 Ala Thr Leu Val Thr Gln Ala Gln Gln Gln Gln Asp Ser Leu
Ala Ile 85 90 95 Leu Gln Gln Gln Glu Gln Phe Pro Asn Gln Ile Glu
Glu Phe Lys Pro 100 105 110 Ile Thr Leu Asp Asn Leu Glu Asp Leu Pro
Val Met Pro Val Asp Gln 115 120 125 Asn Met Ala Asn Glu Ile Tyr Arg
Val Ala Glu Glu Ala Lys Asn Glu 130 135 140 Ala Gln Asn Phe Gln Asn
Gly Thr Gln Lys Gln Pro Glu Met Val Val 145 150 155 160 Ser Asp Ala
Ser Gln Ala Glu Leu His Glu Ile Asn Gln Ala Pro Val 165 170 175 Asn
Ile Asp Gln Leu Met His Glu Ile Gln Ser Asp Ser Lys Ile Val 180 185
190 Val Glu Ala Asn Glu Thr Gly Lys Thr Leu Pro Glu Leu Thr Ala Ala
195 200 205 Val Glu Glu Pro Pro Glu Glu Lys Gly Phe Phe Arg Arg Ile
Phe Asn 210 215 220 Lys Ile Arg Pro Pro Arg Val Ile Pro Met Glu Gln
Ile Pro Arg Ile 225 230 235 240 Thr Ala Glu Val Thr Gly Ala Pro Asp
Asp Leu Ala Lys Asn Ile Lys 245 250 255 Gly Lys Leu Ser Thr Phe Thr
Gln Glu Ser Phe Glu Asp Phe Asn Ala 260 265 270 Ala Leu Pro Gln Leu
Arg Ser Leu Ser Asn Gln Ala Ala Gln Ala Val 275 280 285 Gly Tyr Tyr
Asn Ala Glu Phe Arg Phe Glu Lys Leu Ser Ala Ser Arg 290 295 300 Val
Arg Val Asn Val Thr Pro Asn Glu Pro Val Arg Ile Asn Glu Gln 305 310
315 320 Asn Ile Glu Phe Thr Gly Ala Gly Ala Lys Gln Pro Gln Phe Gln
Val 325 330 335 Ile Arg Leu Val Pro Asp Gln Asp Val Gly Asp Ile Phe
Asn His Gly 340 345 350 Leu Tyr Glu Thr Thr Lys Ser Arg Ile Val Asp
Ala Ala Ser Asp Asn 355 360 365 Gly Tyr Phe Asp Ala Tyr Trp Arg Leu
His Asp Val Lys Val Ser Gln 370 375 380 Pro Glu Asn Lys Ala Asp Ile
Asn Leu Lys Tyr Glu Thr Gly Glu Arg 385 390 395 400 Tyr Lys Leu Gly
Lys Val Glu Phe Arg Met Ser Asp Pro Ser Lys Pro 405 410 415 Leu Pro
Leu Asn Met Asn Ile Leu Glu Ser Met Ala Pro Trp Lys Glu 420 425 430
Gly Asp Asp Tyr Ala Phe Trp Arg Val Asn Val Leu Ala Asn Asn Leu 435
440 445 Thr Asn Ser Arg Tyr Phe Asn Tyr Thr Leu Val Asp Ser Ile Lys
Pro 450 455 460 Asp Pro Ile Glu Lys Pro Leu Glu Leu Pro Pro Asp Leu
Gln Ala Leu 465 470 475 480 Val Asp Gln Gln Asn Val Asp Ile Asp Glu
Ser Lys Leu Leu Pro Leu 485 490 495 Glu Gln Gln Gln Leu Ala Lys Ala
Arg Gln Leu Ala Ser Ser Ser Lys 500 505 510 Glu Val Thr Gln Asn Val
Val Asp Glu Lys Gln Phe Ala Gly Thr Glu 515 520 525 Ser Val Gln Ala
Ala Pro Ala Ser Leu Lys Ala Ala Thr Val Gln His 530 535 540 Glu Glu
Gln Glu Ser Glu Gln Asp Arg Leu Gln Ala Gln Ala Arg Glu 545 550 555
560 Glu Lys Arg Ile Pro Val Ile Val Thr Leu Asn Ala Asp Lys Leu Asn
565 570 575 Ser Leu Glu Thr Gly Ile Gly Tyr Gly Thr Asp Thr Gly Ala
Arg Leu 580 585 590 Arg Ser Gln Tyr Arg Arg Ser Ile Val Asn Lys Tyr
Gly His Ser Phe 595 600 605 Asp Ala Asn Leu Glu Leu Ser Gln Ile Arg
Gln Ser Ile Asp Gly Arg 610 615 620 Tyr Ser Ile Pro Tyr Lys His Pro
Leu Asn Asp Tyr Phe Asn Ile Val 625 630 635 640 Gly Gly Tyr Glu Arg
Glu Thr Arg Asp Asp Ile Gly Pro Asp Val Ser 645 650 655 Leu Leu Thr
Glu Ser Ala Val Leu Gly Gly Glu Arg Val Ile Lys Lys 660 665 670 Pro
Leu Gly Asn Trp Gln His Thr Ile Gly Val Arg Tyr Arg Leu Asp 675 680
685 Arg Leu Thr Gln Lys Gly Asn Val Asp Ile Ser Glu Leu Pro Asp Ala
690 695 700 Phe Lys Thr Ala Ala Ser Glu Gln Glu Ala Leu Leu Phe Ser
Tyr Glu 705 710 715 720 Thr Ser Lys Thr Ser Ser Asn Thr Arg Leu Asn
Pro Thr Lys Ala Phe 725 730 735 Lys Gln Thr Tyr Lys Leu Glu Leu Gly
Ser Glu Ser Leu Leu Ser Asp 740 745 750 Ala Asn Met Ala Ile Ala Thr
Ala Gly Trp Arg Phe Ile Tyr Ser Leu 755 760 765 Gly Glu Asn Asp Asp
His Gln Phe Val Gly Arg Ser Asp Phe Ser Tyr 770 775 780 Ile Phe Thr
Asp Glu Phe Asp Lys Val Pro Tyr Asn Leu Arg Phe Phe 785 790 795 800
Thr Gly Gly Asp Gln Thr Ile Arg Gly Phe Asp Tyr Lys Ser Leu Ser 805
810 815 Pro Glu Asp Asn Gly Tyr Lys Ile Gly Gly Gln Ala Leu Ala Val
Gly 820 825 830 Ser Leu Glu Tyr Asn Tyr Gln Phe Lys Glu Gly Trp Arg
Ala Ala Val 835 840 845 Phe Ser Asp Phe Gly Asn Ala Tyr Asp Lys Ser
Phe Ser Asn Pro Thr 850 855 860 Ala Tyr Ser Val Gly Val Gly Ile Arg
Trp Lys Ser Pro Ile Gly Pro 865 870 875 880 Ile Arg Leu Asp Val Ala
Ser Gly Ile Ser Asp Asp Asn His Pro Ile 885 890 895 Arg Leu His Phe
Phe Ile Gly Pro Gln Leu 900 905 25974PRTAcinetobacter baumannii
25Met Phe Ile Lys Ser Ile Leu Ser Ser Ile Thr Ser Ile Ile Pro Leu 1
5 10 15 Pro Glu Asn Ser Asn Thr Ser Ser Asn Leu Gly Asn Gly Ser Gly
Asp 20 25 30 Gly Leu Leu Asn Gly Ile Ser Ser Gly Asn Gly Glu His
Asn Tyr Gly 35 40 45 Ile Gly Asn Gly Ile Ala Asp Asp Ala Ser Ile
Thr Ala Pro Ile Thr 50 55 60 Ile Pro Leu Asn Leu Ser Gly Asn Ser
Ile Thr Leu Ile Gly Asn Ser 65 70 75 80 Ser Ser Ser Ser Val Asn Ser
Ser Pro Thr Thr Thr Ser Asn Asn Val 85 90 95 Asn Asp Asn Asp Val
Thr Asn Asn Gly Asn Gly Ser Thr Ile Gly Ser 100 105 110 Gly Thr Gly
Asn Gly Ser Gly Asp Gly Leu Leu Asn Gly Ala Ala Ser 115 120 125 Gly
Asn Gly Glu His Asn Tyr Gly Ile Gly Asn Gly Ile Ala Asp Asp 130 135
140 Ala Ser Ile Thr Ala Pro Leu Ser Ile Pro Ile Asn Leu Ala Gly Asn
145 150 155 160 Ser Ile Thr Leu Ile Gly Asp Ser Ser Ser Ser Ser Val
Asn Asn Ser 165 170 175 Ala Thr Asn Thr Ser Asn Thr Val Asn Asp Asn
Asp Thr Thr Tyr Asn 180 185 190 Gly Asn Gly Ser Gly Gly Gly Asn Gly
Ser Gly Asp Gly Leu Leu Asn 195 200 205 Gly Ile Gly Ser Gly Asn Gly
Glu Gln Asn Tyr Gly Ile Gly Asn Gly 210 215 220 Ile Ala Asp Asp Ala
Ser Ile Thr Ala Pro Ile Thr Leu Pro Ile Asn 225 230 235 240 Leu Ser
Gly Asn Ser Ile Thr Leu Ile Gly Asn Ser Ser Ala Ser Ser 245 250 255
Val Asn Ser Ser Pro Thr Thr Thr Ser Asn Thr Val Asn Asp Asn Asp 260
265 270 Thr Thr Tyr Asn Gly Asn Gly Thr Gly Asp Ser Gly Val Ser Ala
Leu 275 280 285 Gly Gly Ser Gly Asn Gly Ser Gly Asp Gly Ala Gly Asn
Gly Ile Ala 290 295 300 Ser Gly Asn Gly Glu His Asn Tyr Gly Ile Gly
Asn Gly Asn Gly Asp 305 310 315 320 Asp Val Asp Ile Thr Ala Pro Ile
Thr Gly Val Leu Asn Ile Ser Gly 325 330 335 Asn Ser Phe Thr Leu Ile
Gly Asn Ser Ser Ser Ser Ser Val Asn Thr 340 345 350 Ala Pro Thr Thr
Thr Ser Asn Thr Val Asn Asp Asn Asp Thr Ile Asp 355 360 365 Asn Gly
Asn Ser Gly Gly Thr Gly Ser Gly Ser Gly Asn Gly Ser Gly 370 375 380
Asp Gly Leu Leu Asn Gly Ala Ala Ser Gly Asn Gly Glu His Asn Tyr 385
390 395 400 Gly Ile Gly Asn Gly Asn Gly Asp Asp Val Asp Ile Thr Ala
Pro Ile 405 410 415 Thr Gly Val Phe Asn Phe Ser Gly Asn Ser Phe Ser
Ile Ile Gly Asn 420 425 430 Ser Ser Ser Ser Ser Ile Asn Thr Ala Pro
Thr Thr Thr Thr Asn Thr 435 440 445 Val Asn Asp Asn Asp Val Thr Asp
Asn Gly Asn Asp Gly Gly Gly Leu 450 455 460 Val Gly Gly Ser Ser Gly
Asn Gly Ser Gly Asp Gly Leu Leu Asn Gly 465 470 475 480 Ala Ala Ser
Gly Asn Gly Glu His Asn Tyr Gly Ile Gly Asn Gly Asn 485 490 495 Gly
Asp Asp Ala Asp Phe Thr Phe Pro Leu Thr Gly Val Leu Asn Phe 500 505
510 Ser Gly Asn Ser Leu Ser Gly Phe Gly Ser Ser Ser Ser Asp Ser Val
515 520 525 Asn Val Ala Pro Thr Thr Ala Thr Asn Thr Val Asn Asp Asn
Asp Thr 530 535 540 Ile Asp Asn Ala Asn Thr Gly Gly Leu Gly Asp Gly
Ser Gly Asn Gly 545 550 555 560 Ser Gly Asp Gly Leu Leu Asn Gly Ala
Ala Ser Gly Asn Gly Glu His 565 570 575 Asn Tyr Gly Ile Gly Asn Gly
Asn Gly Asp Asp Ala Asp Phe Thr Leu 580 585 590 Pro Phe Thr Gly Gly
Leu Asn Ile Leu Gly Asn Ala Leu Ser Gly Ile 595 600 605 Gly Gly Ser
Ser Thr Asp Ser Ile Asn Ile Ser Pro Thr Thr Thr Ser 610 615 620 Asn
Thr Val Asn Asp Asn Asp Thr Thr Asn Asn Gly Asn Thr Ser Gly 625 630
635 640 Gly Val Ile Gly Ser Gly Asp Ser Gly Asn Gly Ser Gly Asp Gly
Leu 645 650 655 Leu Asn Gly Ile Ser Ser Gly Asn Gly Glu His Asn Tyr
Gly Ile Gly 660 665 670 Asn Gly Asn Gly Asp Asp Val Asp Val Val Ala
Pro Ile Thr Thr Pro 675 680 685 Leu Asn Val Leu Gly Asn Ser Phe Ser
Phe Ile Gly Gly Glu Gly Thr 690 695 700 Gly Asp Ile Leu Gly Pro Ile
Thr Gly Ile Ile Gly Gly Ile Gly Gly 705 710 715 720 Asp Gly Asp Ile
Leu Ser Pro Ile Thr Gly Ile Ile Gly Gly Ile Gly 725 730 735 Gly Asp
Gly Asp Ile Leu Ser Pro Ile Thr Gly Ile Ile Gly Ser Ile 740 745 750
Gly Gly Ile Gly Gly Asp Leu Gly Asp Asn Pro Leu Thr Gly Ile Ile 755
760 765 Gln Ser Gly Ile Asp Val Leu Gln Asn Leu Glu Ser Leu Lys Thr
Gly 770 775 780 Leu Ile Asn Thr Gly Ile Asp Thr Ile Ala Gly Thr Ile
Ile Gly Val 785 790 795 800 Phe Pro Asp Ala Glu His Pro Val Gly Asp
Phe Ala Asp Leu Gly Lys 805 810 815 Leu Leu Phe Glu Thr Ser Arg Asp
Ser Val Asn Gly Thr Leu Glu Ala 820 825 830 Ile Ser Asp Leu Ala Gly
Ala Asp Leu Glu Gly Ala Ser Gly Ser Ile 835 840 845 Thr Gly Val Ile
Asp Thr Leu Ile Thr Asn Gly Ser Thr Ala Ser Thr 850 855 860 Ile Ile
Gln His Ile Val Gly Asp Asp Leu Val Thr Glu Asn Gly Gly 865 870 875
880 Leu Leu Gly Ser Ile Thr Thr Ile Ile Gly Gly Val Asp Ser Gly Asp
885 890 895 Gly Gly Leu Leu Gly Gly Leu Asp Gly Leu Ile Ser Ile Asn
Tyr Gly 900 905 910 Asp Ser Asp Asn Ser Asn Ser Ile Asp Val Glu Asp
Ile Leu Gly Asn 915 920 925 Ile Leu Gly Ser Val Gly Ser Asn Gln Gly
Ile Ala Val Gly Glu Pro 930 935 940 Asp Pro Thr Gly Gly Ser Leu Ile
His Thr Ile Ser Leu Asn Thr Val 945 950 955 960 Asn Gln Leu Thr Asp
Gln Leu Leu His Ala Leu Pro Thr Val 965 970 261071PRTAcinetobacter
baumannii 26Met Tyr Lys Pro Thr Thr Phe Val Trp Gln Pro Ser Ala Ala
Ser Leu 1 5 10 15 Phe Lys Ile Thr Val Leu Ser Ser Ala Leu Ala Ala
Leu Gly Ile Thr 20 25 30 Thr Gly Cys Ser Ser Thr Pro Gln Ser Ala
Lys Thr Ser Lys Thr Lys 35 40 45 Gln Val Ser Gly Ala Gly Tyr Leu
Asp Ala Ser Ser Leu Asp Ser Leu 50 55 60 Glu Asp Leu Leu Ser Ala
Thr Asp Met Arg Ala Val Glu Gly Asp Arg 65 70 75 80 Leu Leu Ile Leu
Lys His Gly Asp Val Trp Lys Arg Met Ala Val Gly 85 90 95 Phe Lys
Met Asp Leu Asn His Trp Asp Pro Arg Ile Glu Ala Gln Arg 100 105 110
Ser Trp Phe Ile Ser Arg Gln Pro Tyr Leu Asp Arg Leu Ser Ala Arg 115
120 125 Ala Ser Arg Tyr Leu Tyr His Thr Val Lys Glu Ala Glu Arg Arg
Gly 130 135 140 Leu Pro Thr Glu Leu Ala Leu Leu Pro Val Ile Glu Ser
Ser Tyr Asp 145 150 155 160 Pro Ala Ala Thr Ser Ser Ala Ala Ala Ala
Gly Leu Trp Gln Phe Ile 165 170 175 Pro Ser Thr Gly Arg Ile Tyr Gly
Leu Gln Gln Thr Gly Met Tyr Asp 180 185 190 Gly Arg Arg Asp Val Val
Glu Ser Thr Arg Ala Ala Tyr Glu Phe Leu 195 200 205 Gly Ser Leu Tyr
Asn Gln Phe Gly Ser Trp Glu Leu Ala Leu Ala Ala 210 215 220 Tyr Asn
Ala Gly Pro Gly Arg Ile Gln Gln Ala Ile Asn Arg Asn Gln 225 230 235
240 Ala Ala Gly Leu Pro Thr Asp Tyr Trp Ser Leu Lys Leu Pro Gln Glu
245 250 255 Thr Met Asn Tyr Val Pro Arg Phe Leu Ala Val Ala Gln Ile
Ile Lys 260 265 270 Asn Pro Arg Ala Tyr Gly Val Ser Leu Pro Pro Ile
Ala Asn Arg Pro 275 280 285 His Phe Arg Glu Val Thr Leu Ser Ala Pro
Leu Ser Leu Asn Glu Ile 290 295 300 Ala Ser Val Thr Gly Leu Ser Arg
Ala Glu Leu Tyr Ala Leu Asn Pro 305 310 315 320 Gly Tyr Arg Gly Glu
Thr Val Asp Pro Ala Ser Pro Met Arg Ile Leu 325 330 335 Ile Pro Ala
Asp Ile Ser Pro Ser Val Asp Asn Lys Leu Lys Gly Met 340 345 350 Lys
Ala Gly Gly Ser Ser Gly Trp Trp Ala Ser Val Thr Ser Pro Ser 355 360
365 Lys Pro Thr Thr Thr Thr Ser Thr Ser Val Thr Val Arg Thr Thr Pro
370 375 380 Ser Thr Pro Ala Gln Pro Val Arg Pro Ser Thr Pro Ala Lys
Thr Ser 385 390 395 400 Ser Ser Ser Val Thr Val Lys Thr Thr Thr Pro
Arg Gly Ser Asp Ala 405 410 415 Leu Ala Ala Phe Ala Ala Ser Ala Asp
Val Pro Ser Ala Pro Arg Ile 420 425 430 Pro Val Ala Val Thr Pro Ala
Ala Asn Ile Lys Pro Val Arg Thr Glu 435 440 445 Pro Pro Ile Ser Ala
Thr Glu Arg Glu Lys Ile Leu Ala Ala Val Arg 450 455 460 Ala Glu Gly
Glu Lys
Glu Thr Val Asp Gln Ala Leu Glu Pro Gln Ala 465 470 475 480 Thr Gln
Ala Glu Lys Asp Gln Val Val Ala Glu Leu Lys Ala Leu Ala 485 490 495
Pro Gln Gly Thr Glu Ile Val Asp Pro Tyr Asp Gly Lys Ile Lys Leu 500
505 510 Thr Ala Ile Gln Thr Ser Gln Ser Val Ala Glu Gln Gln Gly Lys
Glu 515 520 525 Val Ser Lys Gly Phe Ala Tyr Pro Lys Thr Leu Ala Glu
Asp Ala Thr 530 535 540 Leu Ala Asn Ser Glu Asp Ala Gln Arg Asn Lys
Asp Lys Pro Tyr Ile 545 550 555 560 Lys Thr Asp Thr Asp Val Val Val
Val Gln Pro Lys Gly Lys Arg Ser 565 570 575 Thr Tyr Thr Val Gln Pro
Gly Asp Thr Leu Ala Val Ile Ala Met Lys 580 585 590 Asn Gly Val Asn
Trp Arg Asp Val Ala Lys Trp Asn Gln Ile Asp Pro 595 600 605 Glu Lys
Thr Leu Phe Val Gly Thr Ser Leu Tyr Leu Tyr Asp Ala Lys 610 615 620
Pro Gln Glu Ala Glu Thr Thr Ala Lys Ser Ala Ala Lys Pro Asp Val 625
630 635 640 Tyr Val Val Gln Ala Asn Asp Ser Leu Thr Gly Val Ala Asn
Gln Phe 645 650 655 Asn Leu Ser Val Lys Gln Leu Ala Glu Tyr Asn Asp
Leu Ser Val Thr 660 665 670 Asp Gly Leu Phe Val Gly Gln Lys Leu Gln
Leu Lys Glu Pro Lys Gly 675 680 685 Asn Arg Ala Ala Lys Val Glu Pro
Lys Ala Ile Gln Ala Ser Thr Arg 690 695 700 Arg Ile Ala Thr Lys Ser
Tyr Thr Val Lys Arg Gly Glu Tyr Leu Lys 705 710 715 720 Leu Ile Ala
Asp Arg Tyr Ala Leu Ser Asn Gln Glu Leu Ala Asp Leu 725 730 735 Thr
Pro Gly Leu Ser Ala Gly Ser Asn Leu Ile Val Gly Gln Lys Ile 740 745
750 Asn Val Pro Ala Lys Glu Ile Thr Val Asp Glu Val Asp Asp Ser Lys
755 760 765 Ala Ser Gly Lys Tyr Glu Lys Leu Ala Ala Gly Pro Ser Tyr
Lys Thr 770 775 780 Glu Ser Tyr Lys Val Gln Arg Gly Asp Thr Leu Ser
Ser Ile Ala Thr 785 790 795 800 Lys Ser Lys Ile Ser Leu Ala Glu Leu
Ala Glu Leu Asn Asn Leu Lys 805 810 815 Ala Asn Ser His Val Gln Leu
Gly Gln Thr Leu Lys Val Pro Ala Gly 820 825 830 Ala Ser Val Pro Asp
Gln Tyr Val Val Gln Ser Gly Asp Ser Leu Asn 835 840 845 Ala Ile Ala
Ala Lys Tyr Asn Leu Gln Thr Ser Tyr Leu Ala Asp Leu 850 855 860 Asn
Gly Leu Ser Arg Thr Ala Gly Leu Arg Ala Gly Gln Arg Leu Lys 865 870
875 880 Leu Thr Gly Glu Val Glu Thr Thr Ser Lys Val Ser Ala Lys Asn
Thr 885 890 895 Lys Glu Glu Thr Pro Glu Thr Tyr Thr Val Lys Ser Gly
Asp Ser Leu 900 905 910 Gly Asn Ile Ala Asn Arg Tyr His Leu Gln Leu
Asp Tyr Leu Ala Ala 915 920 925 Leu Asn Gly Leu Ser Arg Asn Ser Asn
Val Arg Val Gly Gln Arg Leu 930 935 940 Lys Leu Thr Gly Asp Leu Pro
Thr Val Glu Thr Ala Lys Thr Asp Thr 945 950 955 960 Ala Lys Ser Ser
Pro Lys Ala Val Val Ala Gly Lys Asn Thr Glu Lys 965 970 975 Tyr Thr
Val Lys Ala Gly Glu Ser Leu Asn Ala Ile Ala Ser Arg Ala 980 985 990
Gly Ile Ser Val Arg Glu Leu Ala Glu Met Asn Ala Leu Lys Ala Asn 995
1000 1005 Ala Asn Leu Gln Arg Gly Gln Asn Ile Val Ile Pro Lys Thr
Val 1010 1015 1020 Val Glu Tyr Lys Val Lys Arg Gly Asp Thr Leu Ile
Gly Leu Ala 1025 1030 1035 Ser Lys Tyr Gly Leu Glu Thr Thr Leu Leu
Ala Glu Leu Asn Asn 1040 1045 1050 Leu Thr Pro Ser Thr Gln Leu Arg
Ile Gly Asp Ile Ile Lys Val 1055 1060 1065 Pro Asn Leu 1070
271110PRTAcinetobacter baumannii 27Met Lys Arg Met Leu Ile Asn Ala
Thr His Ala Glu Glu Val Arg Val 1 5 10 15 Ala Leu Ile Thr Gly Asn
Arg Leu Tyr Asp Phe Asp Leu Glu Asn Arg 20 25 30 Thr Arg Glu Gln
Lys Lys Ser Asn Ile Tyr Lys Gly His Val Thr Arg 35 40 45 Val Glu
Pro Ser Leu Glu Ala Val Phe Val Glu Tyr Gly Ala Gly Arg 50 55 60
Gln Gly Phe Leu Ser Met Arg Glu Ile Ala Asn Ser Tyr Phe Gln Ala 65
70 75 80 Asp Pro Arg Gln Thr Ser Asn Ile Arg Glu Leu Ile Thr Glu
Gly Thr 85 90 95 Glu Leu Leu Val Gln Val Glu Lys Glu Glu Arg Gly
Asn Lys Gly Ala 100 105 110 Ala Leu Ser Thr Phe Ile Ser Leu Ala Gly
Arg Tyr Leu Val Leu Met 115 120 125 Pro Asn Asn Pro Lys Gly Gly Gly
Ile Ser Arg Gln Ile Ser Gly Ser 130 135 140 Val Arg Glu Glu Leu Lys
Glu Ile Leu Ala Ser Leu Asn Val Pro Arg 145 150 155 160 Gly Met Ser
Val Ile Val Arg Thr Ala Gly Ile Gly Arg Thr Gln Glu 165 170 175 Glu
Leu Gln Leu Asp Leu Gln His Leu Leu Asp Leu Trp Ala Gln Ile 180 185
190 Gln Gly Thr Ala Ser Ser Gly Pro Ser Pro Met Leu Val His Gln Glu
195 200 205 Ala Gly Val Val Thr Arg Ala Ile Arg Asp Tyr Leu Arg Asp
Asp Val 210 215 220 Ala Glu Ile Leu Ile Asp Ser Glu Gln Ala Tyr Asn
Glu Ala Tyr Asn 225 230 235 240 Phe Val Lys Ala Val Met Pro Arg Gln
Leu Asp Lys Leu Lys Thr Tyr 245 250 255 Thr Leu Asn Glu Pro Leu Phe
Ala His Phe Gly Ile Glu Ser Gln Ile 260 265 270 Gln Thr Ala Tyr Glu
Arg Glu Val Lys Leu Pro Ser Gly Gly Ser Ile 275 280 285 Val Ile Asp
Gln Thr Glu Ala Leu Val Ser Ile Asp Ile Asn Ser Ala 290 295 300 Lys
Ser Thr Arg Gly His Asp Val Glu Glu Thr Ala Leu Asn Thr Asn 305 310
315 320 Leu Glu Ala Ala Glu Glu Ile Ala Arg Gln Leu Arg Leu Arg Asp
Ile 325 330 335 Gly Gly Leu Val Val Ile Asp Phe Ile Asp Met Thr Lys
Glu Arg Asn 340 345 350 Gln Arg Met Val Glu Ala Lys Leu Arg Glu Ala
Thr Gln Ser Asp Arg 355 360 365 Ala Arg Ile Gln Phe Gly Gln Leu Ser
Arg Phe Gly Leu Met Glu Met 370 375 380 Ser Arg Gln Arg Leu Arg Pro
Ser Leu Glu Glu Ala Thr Gly Tyr Val 385 390 395 400 Cys Pro Arg Cys
His Gly Thr Gly Met Val Arg Asp Leu Arg Ser Leu 405 410 415 Ser Leu
Ser Ile Met Arg Lys Val Glu Glu Ile Ala Leu Arg Glu Arg 420 425 430
His Gly Glu Val Gln Val Glu Val Pro Val Glu Ile Ala Ala Phe Leu 435
440 445 Leu Asn Glu Lys Arg His Ser Leu Val Tyr Leu Glu Gln Thr Ser
Gly 450 455 460 Val Arg Val Thr Val Leu Pro His Pro His Leu Glu Thr
Pro His Tyr 465 470 475 480 Glu Ile Ala Tyr Asn Pro Asp Gly Phe Ala
Pro Ser Ser Tyr Glu Arg 485 490 495 Thr Glu Ala Thr Arg Ser Ser Glu
Lys Glu Leu Gly Tyr Glu Ser Ser 500 505 510 Glu Trp His Leu Glu Glu
Ala Asp His Gly His Ala His Val Thr Ala 515 520 525 Thr Ala Ser Thr
His Ala Ala Ala Gln Lys Lys Ala Asn His Ala Thr 530 535 540 Gln Pro
Val Ala Gln Pro Ser Ala Gln Lys Ala Ala Ser Pro Cys Ala 545 550 555
560 Trp Leu Glu Asn Leu Phe Val Gln Lys Gln Ala Gln Thr Val Asp Gln
565 570 575 Ser Arg Ser Ala Gln Asn Ala Ala Ala Ala Ile Glu Gln Met
Val Asn 580 585 590 Thr Gly Ala Val Ser Arg Gly Gln Phe Gly Gln Val
Ala Val Pro Ala 595 600 605 Val Ala Glu Val Ala Pro Val Gln Ser Asn
Asn Ala Tyr Ile Ser Gln 610 615 620 Ser Pro Val Lys Gln Asp Val Arg
Glu His Val Glu Lys Asp Asp Lys 625 630 635 640 Ser Gln Gln Gln Arg
Gln Asn Asn Lys Lys Arg Lys His Lys Glu Gln 645 650 655 Arg Glu Gln
His His Gln Ser His Glu Gln Gln His Gln Val His Glu 660 665 670 Glu
Val Val Gln Leu Ser Arg Gln Glu Gln Arg Glu Leu Lys Arg Gln 675 680
685 Gln Lys Arg Gln Gln Gln Gln Asp Gln Gln His Gln Asn Asn Asp Val
690 695 700 Gln His Thr Glu Asn Ala Val Pro Arg Arg Asp Arg Asn Asn
Gln Gln 705 710 715 720 Arg Pro Asn Arg Pro Asn Arg His Arg Asp Pro
Ser Val Leu Asn Glu 725 730 735 Asn Gln Asn Thr Leu Val Val Val Asp
Glu Lys Gln Ile Lys Val Asp 740 745 750 Val Ile Asp Ala Pro Lys His
Asp Val Met Asn Thr Ala Leu Ile Ile 755 760 765 Asn Val Asp Gln Gly
Gln Ser Glu Ile Val Ala Leu Thr Pro Glu Arg 770 775 780 Arg His Val
Glu Arg Val Glu Thr Thr Ser Thr Glu Val Ala Gln Glu 785 790 795 800
Pro Thr Pro Ala Pro Val Val Ala Glu Lys Ala Ala Val Val Glu Thr 805
810 815 Lys Glu Glu Ala Gln Pro Ser Gln Glu Ala Ala Gln Pro Gln Ile
Lys 820 825 830 Arg Ala Ser Asn Asp Pro Arg Met Arg Arg Arg Gln Gln
Arg Glu Ala 835 840 845 Lys His Ala Lys Ala Ala Thr Pro Ser Ile Ala
Pro Ser Gln Ile Pro 850 855 860 Thr Leu Ala Gln His Thr Ile Gly Ser
Leu Ile Arg His Val Tyr Gly 865 870 875 880 Glu Asp Cys Thr Val Leu
Ile Glu Gln Phe Gly Leu Val Pro Thr Phe 885 890 895 Asn Arg Ala Leu
Gln Lys Phe Ala Glu Gln Tyr Ala Ser Thr Leu Val 900 905 910 Val Glu
Val Thr Ala Glu Thr Glu Glu Lys Lys Pro Val Thr Arg Asp 915 920 925
Ala Glu Leu Pro Ser His Lys Pro Ala Glu Glu Ala Glu Pro Ala Pro 930
935 940 Val Leu Pro Leu Thr Pro Pro Gln Ala Pro Ala Pro Arg Val Ala
Asn 945 950 955 960 Asp Pro Arg Glu Arg Arg Arg Leu Ala Lys Leu Ala
Ala Glu Gln Ala 965 970 975 Phe Glu Gln Val Lys Gln Gln His Ser Ala
Gln Glu Glu Val Ala Thr 980 985 990 Pro Ala Pro Val Ala Glu Glu Thr
Val Ala Ala Pro Thr Ala Glu Thr 995 1000 1005 Gln Ala Thr Val Glu
Pro Ala Gln Gln Pro Leu Glu Leu Asn Gln 1010 1015 1020 Ser Thr Glu
Val Val Gln Pro Glu Ala Ala Pro Ala Glu Glu Lys 1025 1030 1035 Ala
Thr Glu Glu Thr Val Ala Glu Ala Pro Ala Ala Lys Glu Pro 1040 1045
1050 Ala Pro Ser Lys Ala Ala Ser Lys Ala Lys Ala Ala Ala Glu Glu
1055 1060 1065 Thr Val Ala Pro Thr Glu Ala Thr Thr Asp Ala Glu Ser
Glu Asp 1070 1075 1080 Val Lys Ala Asp Lys Asp Lys Pro Ser Arg Pro
Arg Arg Pro Arg 1085 1090 1095 Gly Arg Pro Pro Lys Lys Ala Asn Pro
Val Ala Glu 1100 1105 1110 281228PRTAcinetobacter baumannii 28Met
Ser Thr Leu Ala Thr Leu Lys Ala Leu Leu Ala Lys Arg Ile Leu 1 5 10
15 Ile Ile Asp Gly Ala Met Gly Thr Met Ile Gln Arg His Lys Leu Glu
20 25 30 Glu Ala Asp Tyr Arg Gly Glu Arg Phe Ala Asp Trp Ala His
Asp Leu 35 40 45 Lys Gly Asn Asn Asp Leu Leu Val Leu Thr Gln Pro
Gln Ile Ile Gln 50 55 60 Gly Ile His Glu Ala Tyr Leu Asp Ala Gly
Ala Asp Ile Ile Glu Thr 65 70 75 80 Asn Ser Phe Asn Gly Thr Arg Val
Ser Met Ser Asp Tyr His Met Glu 85 90 95 Asp Leu Val Pro Glu Ile
Asn Arg Glu Ala Ala Arg Leu Ala Lys Ala 100 105 110 Ala Cys Glu Lys
Tyr Ser Thr Pro Asp Lys Pro Arg Phe Val Ala Gly 115 120 125 Val Leu
Gly Pro Thr Ser Arg Thr Cys Ser Ile Ser Pro Asp Val Asn 130 135 140
Asn Pro Ala Phe Arg Asn Ile Ser Phe Asp Glu Leu Lys Glu Asn Tyr 145
150 155 160 Ile Glu Ala Thr His Ala Leu Ile Glu Gly Gly Ala Asp Ile
Ile Leu 165 170 175 Ile Glu Thr Val Phe Asp Thr Leu Asn Cys Lys Ala
Ala Ile Phe Ala 180 185 190 Val Lys Glu Val Phe Lys Gln Ile Gly Arg
Glu Leu Pro Ile Met Ile 195 200 205 Ser Gly Thr Ile Thr Asp Ala Ser
Gly Arg Thr Leu Thr Gly Gln Thr 210 215 220 Ala Glu Ala Phe Trp Asn
Ser Val Arg His Gly Asp Leu Leu Ser Ile 225 230 235 240 Gly Phe Asn
Cys Ala Leu Gly Ala Asp Ala Met Arg Pro His Val Lys 245 250 255 Thr
Ile Ser Asp Val Ala Asp Thr Phe Val Ser Ala His Pro Asn Ala 260 265
270 Gly Leu Pro Asn Ala Phe Gly Glu Tyr Asp Glu Thr Pro Glu Gln Thr
275 280 285 Ala Ala Phe Leu Lys Glu Phe Ala Glu Ser Gly Leu Ile Asn
Ile Thr 290 295 300 Gly Gly Cys Cys Gly Thr Thr Pro Asp His Ile Arg
Ala Ile Ala Asn 305 310 315 320 Ala Val Lys Asp Ile Ala Pro Arg Gln
Val Pro Glu Thr Val Pro Ala 325 330 335 Cys Arg Leu Ser Gly Leu Glu
Pro Phe Asn Ile Tyr Asp Asp Ser Leu 340 345 350 Phe Val Asn Val Gly
Glu Arg Thr Asn Val Thr Gly Ser Lys Lys Phe 355 360 365 Leu Arg Leu
Ile Arg Glu Glu Asn Phe Ala Glu Ala Leu Glu Val Ala 370 375 380 Gln
Gln Gln Val Glu Ala Gly Ala Gln Ile Ile Asp Ile Asn Met Asp 385 390
395 400 Glu Gly Met Leu Asp Ser Gln Asn Ala Met Val His Phe Leu Asn
Leu 405 410 415 Val Ala Ser Glu Pro Asp Ile Ser Arg Val Pro Ile Met
Ile Asp Ser 420 425 430 Ser Lys Trp Glu Ile Ile Glu Ala Gly Leu Lys
Cys Val Gln Gly Lys 435 440 445 Pro Val Val Asn Ser Ile Ser Leu Lys
Glu Gly Tyr Asp Glu Phe Val 450 455 460 Glu Lys Ala Arg Leu Cys Arg
Gln Tyr Gly Ala Ala Ile Ile Val Met 465 470 475 480 Ala Phe Asp Glu
Val Gly Gln Ala Asp Thr Ala Glu Arg Lys Arg Glu 485 490 495 Ile Cys
Lys Arg Ser Tyr Asp Ile Leu Val Asn Glu Val Gly Phe Pro 500 505 510
Ala Glu Asp Ile Ile Phe Asp Pro Asn Val Phe Ala Val Ala Thr Gly 515
520 525 Ile Glu Glu His Asn Asn Tyr Ala Val Asp Phe Ile Glu Ala Thr
Gly 530 535 540 Trp Ile Lys Gln Asn Leu Pro His Ala Met Ile Ser Gly
Gly Val Ser 545 550 555 560 Asn Val Ser Phe Ser Phe Arg Gly Asn Glu
Pro Val Arg Glu Ala Ile 565 570
575 His Ser Val Phe Leu Tyr His Ala Ile Lys Gln Gly Met Thr Met Gly
580 585 590 Ile Val Asn Ala Gly Gln Met Ala Ile Tyr Asp Asp Ile Pro
Thr Glu 595 600 605 Leu Lys Glu Ala Val Glu Asp Val Ile Leu Asn Gln
Asn Gln Gly Glu 610 615 620 Ser Gly Gln Ala Ala Thr Glu Lys Leu Leu
Glu Val Ala Glu Lys Tyr 625 630 635 640 Arg Gly Gln Gly Gly Ala Thr
Lys Glu Ala Glu Asn Leu Glu Trp Arg 645 650 655 Asn Glu Ser Val Glu
Lys Arg Leu Glu Tyr Ala Leu Val Lys Gly Ile 660 665 670 Thr Thr Tyr
Ile Asp Gln Asp Thr Glu Glu Ala Arg Leu Lys Ser Lys 675 680 685 Arg
Pro Leu Asp Val Ile Glu Gly Pro Leu Met Asp Gly Met Asn Val 690 695
700 Val Gly Asp Leu Phe Gly Ser Gly Lys Met Phe Leu Pro Gln Val Val
705 710 715 720 Lys Ser Ala Arg Val Met Lys Gln Ala Val Ala Trp Leu
Asn Pro Tyr 725 730 735 Ile Glu Ala Glu Lys Thr Glu Gly Gln Ser Lys
Gly Lys Val Leu Met 740 745 750 Ala Thr Val Lys Gly Asp Val His Asp
Ile Gly Lys Asn Ile Val Gly 755 760 765 Val Val Leu Gly Cys Asn Gly
Tyr Asp Ile Val Asp Leu Gly Val Met 770 775 780 Val Pro Cys Glu Lys
Ile Leu Gln Thr Ala Ile Asp Glu Lys Cys Asp 785 790 795 800 Ile Ile
Gly Leu Ser Gly Leu Ile Thr Pro Ser Leu Asp Glu Met Val 805 810 815
Phe Val Ala Lys Glu Met Gln Arg Lys Gly Phe Asn Ile Pro Leu Leu 820
825 830 Ile Gly Gly Ala Thr Thr Ser Lys Ala His Thr Ala Val Lys Ile
Asp 835 840 845 Pro Gln Tyr Gln Asn Asp Ala Val Ile Tyr Val Ala Asp
Ala Ser Arg 850 855 860 Ala Val Gly Val Ala Thr Thr Leu Leu Ser Lys
Glu Met Arg Gly Ala 865 870 875 880 Phe Ile Glu Glu His Arg Ala Glu
Tyr Ala Lys Ile Arg Glu Arg Leu 885 890 895 Ala Asn Lys Gln Pro Lys
Ala Ala Lys Leu Thr Tyr Lys Glu Ser Val 900 905 910 Glu Asn Gly Phe
Lys Ile Asp Glu Ser Tyr Val Pro Pro Lys Pro Asn 915 920 925 Leu Leu
Gly Thr Gln Val Leu Lys Asn Tyr Pro Leu Ala Thr Leu Val 930 935 940
Asp Tyr Phe Asp Trp Thr Pro Phe Phe Ile Ser Trp Ser Leu Thr Gly 945
950 955 960 Lys Phe Pro Lys Ile Leu Glu Asp Glu Val Val Gly Glu Ala
Ala Thr 965 970 975 Asp Leu Tyr Asn Gln Ala Gln Ala Met Leu Lys Asp
Ile Ile Asp Asn 980 985 990 Asn Arg Phe Asp Ala Arg Ala Val Phe Gly
Met Phe Pro Ala Gln Arg 995 1000 1005 Thr Asp Ala Asp Thr Val Ser
Val Phe Asp Glu Ala Gly Gln Asn 1010 1015 1020 Val Thr His Thr Phe
Glu His Leu Arg Gln Gln Ser Asp Lys Val 1025 1030 1035 Thr Gly Lys
Pro Asn Leu Ser Leu Ala Asp Tyr Ile Arg Ala Asp 1040 1045 1050 Arg
Glu Gln Gln Asp Tyr Leu Gly Gly Phe Thr Val Ser Ile Phe 1055 1060
1065 Gly Ala Glu Glu Leu Ala Asn Glu Tyr Lys Ala Lys Gly Asp Asp
1070 1075 1080 Tyr Ser Ala Ile Leu Val Gln Ser Leu Ala Asp Arg Phe
Ala Glu 1085 1090 1095 Ala Phe Ala Glu His Leu His Glu Arg Ile Arg
Lys Glu Phe Trp 1100 1105 1110 Gly Tyr Lys Ala Asp Glu Gln Leu Ser
Asn Glu Glu Leu Ile Lys 1115 1120 1125 Glu Lys Tyr Val Gly Ile Arg
Pro Ala Pro Gly Tyr Pro Ala Cys 1130 1135 1140 Pro Glu His Ser Glu
Lys Ala Val Leu Phe Asp Trp Leu Gly Ser 1145 1150 1155 Thr Asp Lys
Ile Gly Thr Lys Leu Thr Glu His Phe Ala Met Met 1160 1165 1170 Pro
Pro Ser Ser Val Ser Gly Phe Tyr Tyr Ser His Pro Gln Ser 1175 1180
1185 Glu Tyr Phe Asn Val Gly Lys Ile Ser Gln Asp Gln Leu Glu Asp
1190 1195 1200 Tyr Ala Lys Arg Lys Gly Trp Thr Leu Asp Glu Ala Lys
Arg Trp 1205 1210 1215 Leu Ala Pro Asn Leu Asp Asp Ser Ile Val 1220
1225 291284PRTAcinetobacter baumannii 29Met Lys Leu Lys Leu Lys Asn
Phe Lys Pro Asn Asn Leu Trp Tyr Ala 1 5 10 15 Val Cys Ser Ser Ser
Met Ile Phe Thr Trp Leu Met Thr Ser Ser Val 20 25 30 Val Gln Ala
Ser Asp Leu Gln Ile Tyr Ala Ser Pro Thr Ala Gly Lys 35 40 45 Lys
Thr Ile Val Met Met Leu Asp Thr Ser Gly Ser Met Thr Asn Asn 50 55
60 Ser Tyr Gly Glu Asn Arg Leu Ala Met Leu Lys Asn Gly Met Asn Ala
65 70 75 80 Phe Leu Ala Ser Asn Asn Pro Val Leu Asn Asp Thr Arg Val
Gly Leu 85 90 95 Gly Asn Phe Ser Ala Asn Gly Asp Ser Arg Ser Gly
Gln Ile Leu Val 100 105 110 Ala Ala Ala Pro Leu Gly Asp Ala Ser Thr
Leu Asn Thr Val Gly Ser 115 120 125 Gln Arg Tyr Lys Leu Lys Gln Ala
Val Ala Asn Leu Thr Ala Gly Gly 130 135 140 Ser Thr Pro Ser Ala His
Ala Tyr Ala Glu Ala Ala Ala Tyr Leu Met 145 150 155 160 Gly Thr Thr
Thr Tyr Ser Glu Thr Asn Tyr Ala Ile Arg Lys Asp Ser 165 170 175 Tyr
Ile Lys Arg Val Arg Arg Ser Asp Asn Arg Thr Glu Tyr Ser Tyr 180 185
190 Cys Thr Asn Tyr Arg Asp Ser Gln Ile Asp Thr Ala Asn Leu Trp Gln
195 200 205 Pro Cys Arg Ser Asn Ser Tyr Trp Ser Ser Trp Ser Thr Asn
Asn Pro 210 215 220 Gly Val Asp Asn Ala Thr Ala Tyr Asp Thr Ser Ser
Asp Trp Thr Tyr 225 230 235 240 Tyr Tyr Thr Tyr Tyr Tyr Thr Thr Phe
Asn Tyr Ala Val Ala Asn Ala 245 250 255 Asp Ser Gly Ile Pro Lys Ser
Lys Ser Asn Asp Thr Ala Ser Asn Pro 260 265 270 Asn Ile Val Val Asp
Arg Asn Ala Thr Asn Ser Asn Ala Val Tyr Gln 275 280 285 Ser Pro Leu
Pro Ala Val Ala Asn Arg Gln Ser Cys Asp Gly Gln Gly 290 295 300 Ile
Tyr Phe Leu Ser Asp Gly Glu Pro Asn Asn Thr Thr Asn Thr Arg 305 310
315 320 Ser Ala Ser Val Met Ser Thr Ala Leu Gly Ser Thr Phe Gly Ala
Asp 325 330 335 Phe Asn Cys Ser Gly Gly Leu Ser Asn Thr Thr Ala Asp
Ser Gly Trp 340 345 350 Ala Cys Met Gly Glu Phe Ala Lys Arg Leu Phe
Asp Lys Thr Lys Asn 355 360 365 Pro Ala Gly Val Ser Ile Gln Thr Ala
Phe Val Gly Phe Gly Ser Asp 370 375 380 Phe Ser Ser Leu Asn Ser Ser
Asp Val Lys Asn Ala Cys Arg Leu Ser 385 390 395 400 Ser Arg Thr Gln
Ser Asp Arg Lys Gly Asp Asp Ala Cys Ser Pro Asn 405 410 415 Gln Ser
Thr Asn Ala Val Ala Ala Pro Gly Tyr Gly Asn Gly Gly Phe 420 425 430
Phe Pro Thr Gln Ser Ser Gln Gly Val Thr Asp Ser Val Ile Ala Phe 435
440 445 Ile Asn Asn Leu Asp Lys Val Pro Leu Glu Pro Leu Thr Thr Gly
Ala 450 455 460 Ile Ser Val Pro Tyr Asp Ala Leu Asn Pro Lys Asn Leu
Gln Glu Tyr 465 470 475 480 Gly Tyr Leu Arg Ala Phe Glu Pro Asn Pro
Ala Asn Thr Tyr Leu Thr 485 490 495 Trp Arg Gly Asn Leu Lys Lys Tyr
His Val Val Leu Ser Gly Ala Asn 500 505 510 Ala Gly Ala Phe Glu Ala
Asn Ser Gly Gly Leu Val Tyr Asn Ala Ser 515 520 525 Gly Ala Phe Arg
Thr Gly Thr Lys Asp Tyr Trp Asn Ser Ser Thr Tyr 530 535 540 Thr Asp
Gly Gly Lys Val Phe Leu Gly Gly Ser Tyr Ala Asn Val Pro 545 550 555
560 Leu Pro Ile Ala Gly Gln Pro Glu Thr Arg Asp Ala Glu Gly Asn Ile
565 570 575 Thr Lys Tyr Tyr Tyr Ala Val Gln Ser Lys Ile Arg Asn Leu
Phe Thr 580 585 590 Asp Val Ser Ala Val Ala Ala Asp Gly Ser Leu Thr
Lys Ile Ser Thr 595 600 605 Ser Gly Thr Asn Leu Leu Lys Ile Pro Ala
Ala Pro Pro Glu Glu Thr 610 615 620 Asn Pro Phe Asp Thr Val Ala Asn
Thr Ala Ser Tyr Val Leu Gly Lys 625 630 635 640 Phe Asp Pro Ser Thr
Gly Gln Asn Ile Leu Lys Ala Phe Pro Ile Ser 645 650 655 Leu Lys Leu
Lys Ile Leu Asn Tyr Leu Gly Tyr Ser Thr Asp Ile Asn 660 665 670 Ala
Thr Thr Leu Pro Ser Ser Leu Val Thr Ser Asn Glu Pro Tyr Leu 675 680
685 Ser Met Gly Gly Ser Ile His Ser Leu Pro Val Gln Leu Thr Tyr Asn
690 695 700 Gly Thr Leu Asp Asp Asn Gly Asn Leu Thr Ser Ala Arg Glu
Gln Ser 705 710 715 720 Ile Leu Tyr Gly Thr Met Glu Gly Gly Leu His
Ile Val Asp Ala Ser 725 730 735 Ser Gly Ile Glu Gln Met Val Phe Val
Pro Ala Asp Ile Leu Asn Asp 740 745 750 Ser Val Ala Ser Lys Ala Leu
Val Val Gly Gln Ser Asp Ala Ser Ala 755 760 765 Pro Ala His Gly Met
Asp Gly Ala Trp Val Ser Asp Pro Ala Tyr Asn 770 775 780 Ile Thr Thr
Val Gly Ser Gly Ser Ser Ala Val Ser Lys Val Thr Ala 785 790 795 800
Lys Gln Met Asn Ile Tyr Gly Gly Met Arg Met Gly Gly Ser Ser Tyr 805
810 815 Tyr Gly Leu Asp Val Leu Ser Pro Thr Ser Pro Lys Leu Leu Phe
Arg 820 825 830 Ile Gly Ala Asp Gln Asn Asp Tyr Ser Arg Met Gly Gln
Ser Trp Ser 835 840 845 Lys Pro Val Leu Ala Asn Ile Arg Tyr Asn Gly
Ser Ile Arg Arg Val 850 855 860 Leu Ile Val Gly Gly Gly Tyr Asp Gln
Cys Tyr Glu Lys Pro Asn Ile 865 870 875 880 Thr Leu Thr Asp Ala Cys
Phe Thr Asn Gly Lys Ala Lys Gly Asn Ala 885 890 895 Val Tyr Ile Ile
Asp Ala Lys Thr Gly Gln Arg Leu Trp Trp Thr Ser 900 905 910 Asp Thr
Gly Ser Asn Thr Asp Asn Ala Asn Met Lys His Ser Ile Val 915 920 925
Ser Arg Ile Ser Thr Leu Asp Arg Asp Ala Asp Gly Leu Val Asp His 930
935 940 Leu Tyr Phe Gly Asp Leu Gly Gly Gln Ile Phe Arg Val Asp Leu
Asn 945 950 955 960 Asn Asn Gln Thr Lys Thr Asn Ser Thr Tyr Ser Ser
Phe Gly Val Arg 965 970 975 Val Val Arg Leu Ala Asn Leu Ala Thr Asn
Asp Ser Thr Tyr Asp Gly 980 985 990 Thr Asn Asp Tyr Thr Gly Gly Asn
Ala Pro Arg Phe Tyr Glu Pro Pro 995 1000 1005 Thr Val Thr Ile His
Asp Tyr Gly Ile His Thr Phe Ile Thr Val 1010 1015 1020 Gly Ile Ala
Ser Gly Asp Arg Ser Thr Pro Leu Asp Val Tyr Pro 1025 1030 1035 Leu
Thr Gly Arg Glu Gly Met Thr Pro Ala Ser Ala Leu Ser Gly 1040 1045
1050 Arg Pro Val Asn Asn Val Tyr Gly Ile Ile Asp Arg Asp Phe Val
1055 1060 1065 Lys Lys Asn Leu Met Ser Leu Thr Asp Asn Gln Leu Glu
Thr Lys 1070 1075 1080 Asp Ile Thr Arg Thr Gly Leu Arg Lys Asn Pro
Gln Ile Leu Arg 1085 1090 1095 Thr Gly Glu Thr Arg Val Ala Gln Ile
Phe Phe Pro Thr Thr Gly 1100 1105 1110 Val Gly Lys Gly Gly Trp Tyr
Arg Ser Leu Ser Ser Thr Ser Asp 1115 1120 1125 Gly Thr Glu Lys Ala
Asn Asn Ser Phe Arg Ile Lys Gly Gly Leu 1130 1135 1140 Lys Ala Phe
Glu Glu Pro Met Ala Ile Thr Gly Asn Leu Ile Ile 1145 1150 1155 Leu
Val Tyr Asp Pro Gln Gly Thr Gly Ile Val Ala Ala Asp Pro 1160 1165
1170 Cys Leu Pro Arg Val Val Gly Glu Thr Asp Arg Gln Thr Tyr Cys
1175 1180 1185 Leu Pro Phe Gly Ala Cys Leu Asn Ser Asp Gly Ser Ile
Asp Gln 1190 1195 1200 Asn Lys Glu Asn His Ser Gly Phe Glu Thr Gln
Thr Gly Thr Asn 1205 1210 1215 Cys Pro Val Gly Ala Ser Glu Cys Asn
Lys Asn Val Ile Gly Ser 1220 1225 1230 Gly Ile Arg Ser Val Thr Phe
Val Pro Thr Glu Asp Asn Pro Pro 1235 1240 1245 Thr Thr Asn Ser Cys
Gly Lys Leu Lys Leu Ser Gly Asn Glu Gln 1250 1255 1260 Gly Thr Gly
Gln Trp Gln Cys Thr Ser His Leu Val Pro Thr Arg 1265 1270 1275 Trp
Tyr Glu Arg Tyr Arg 1280 303047PRTAcinetobacter baumannii 30Met Thr
Asp Ala Ala Gly Asn Thr Ser Glu Gln Ala Val Gln Lys Val 1 5 10 15
Val Val Asp Thr Thr Ala Pro Gln Ala Gly Glu Leu Thr Leu Ser Asp 20
25 30 Leu Ser Asp Thr Gly Ile Ser Ala Thr Asp Gln Ile Thr Gln Asp
Lys 35 40 45 Asn Phe Asn Leu Lys Leu Glu Gly Gln Glu Ser Gly Ser
Arg Val Thr 50 55 60 Tyr Leu Val Ser Thr Asp Glu Gly Lys Thr Trp
Gln Glu Thr Thr Ile 65 70 75 80 Ala Gln Lys Asp Leu Thr Asp Gly Val
Tyr Gln Tyr Lys Ala Val Val 85 90 95 Thr Asp Ala Ala Gly Asn Thr
Ser Glu Thr Ala Val Gln Lys Val Val 100 105 110 Val Asp Thr Thr Thr
Pro Gln Ala Gly Glu Leu Thr Leu Ser Asp Leu 115 120 125 Asn Asp Thr
Gly Val Ser Val Thr Asp Gln Ile Thr Gln Asp Lys Asn 130 135 140 Phe
Asn Leu Lys Leu Glu Gly Gln Glu Thr Gly Ser Arg Val Thr Tyr 145 150
155 160 Leu Val Ser Thr Asp Glu Gly Lys Thr Trp Gln Glu Thr Thr Ile
Ala 165 170 175 Gln Lys Asp Leu Ala Asp Gly Val Tyr Lys Tyr Lys Ala
Val Val Thr 180 185 190 Asp Ala Ala Gly Asn Thr Ser Glu Thr Ala Val
Gln Lys Val Val Val 195 200 205 Asp Thr Thr Ala Pro Gln Ala Gly Lys
Leu Thr Leu Ser Asp Leu Asn 210 215 220 Asp Thr Gly Val Ser Ala Thr
Asp Gln Ile Thr Gln Asp Asn Ser Phe 225 230 235 240 Thr Leu Lys Leu
Ala Gln Pro Ile Val Ile Gly Glu Gln Ala Ala Leu 245 250 255 Leu Asp
His Tyr Glu Val Ser Lys Asp Glu Gly Lys Thr Trp Gln Glu 260 265 270
Thr Thr Ala Asp Gln Lys Asp Leu Ala Asp Gly Ile Tyr Gln Tyr Lys 275
280 285 Ala Ile Val Thr Asp Leu Ala Gly Asn Ile Ser Glu Ser Ala Ile
Gln 290 295 300 Lys Val Val Val Asp Asn Ser Leu Asn Val Glu Ser Thr
Thr Val Ile 305 310 315 320 Val Lys Pro Ile Thr Glu Asp Asn Thr Ile
Ser Leu Val Glu Lys Asp 325 330
335 Gln Val Ile Ser Ile Arg Leu Glu Ile Ala Asn Leu Pro Thr Asp Leu
340 345 350 Asn Ser Ser Leu Thr Ser Val Asn Thr Thr Leu Gly Asn Val
Thr Tyr 355 360 365 Asn Phe His Phe Asp Glu Val Thr Gln Glu Trp Val
Thr Glu Ile Pro 370 375 380 Ala Glu Phe Leu Trp Ser Val Glu Pro Gln
Thr Asn Ile Ser Ile Glu 385 390 395 400 Ile Ser Leu Thr Asp Gln Ala
Gly Asn Thr Ala Ile Ile Lys His Thr 405 410 415 Gln Asn Tyr Asn Val
Asp His Thr Pro Asn Ser Pro Thr Leu Asp Ser 420 425 430 Leu Thr Phe
Asn Asn Ile Asp Gly Ala Ile Ile Ser Gly Ser Ala Tyr 435 440 445 Lys
Gly Ser Lys Val Asp Ile Tyr Asn Lys Asn Gly Asp Trp Leu Ala 450 455
460 Ser Thr Ile Thr Asn Glu Glu Gly Lys Phe Thr Leu Gln Asp Leu Ser
465 470 475 480 Ile Asn Ser Asn Gln Glu Val Tyr Ala Val Ala Thr Tyr
Asn Gly Tyr 485 490 495 Ser Ser Glu Asn Ser Ser Ile Gly Leu Val Thr
Glu Val Pro Ala Ile 500 505 510 Ser Ile Thr Arg Ile Ser Pro Glu Gly
Val Ile Ser Gly Tyr Ala Thr 515 520 525 Glu Gly Ser His Phe Ile Val
Lys Asp Gln Asn Gly Asn Ile Leu Gln 530 535 540 Glu Phe Asn Ser Asn
Val Phe Asp Ser Ser Gly Ile Thr Pro Phe Ser 545 550 555 560 Val Met
Ala Leu Gly Glu Val Arg Pro Phe Ile Leu Ser Leu Asp Gln 565 570 575
Pro Leu Glu Glu Gly Ala Gln Ile Ile Ile Ser Ile Asp Lys Asp Asn 580
585 590 Ile Ser Gly His Pro Gln Tyr Ile Thr Ala Asp Tyr Thr Pro Ala
Val 595 600 605 Phe Leu Glu Thr Pro Gln Phe Asp Ile Ser Gly Glu Thr
Leu Ser Val 610 615 620 His Val Asn Glu Pro Asn Ser Phe Ile Arg Ala
Phe Ser Gly Glu Gly 625 630 635 640 Asn Leu Ile Ala Thr Gly Phe Thr
Asp Glu Gln Gly Phe Ala Ser Leu 645 650 655 Gln Val Phe Gln Phe Leu
Lys Glu Gly Glu Thr Val Ser Val Gln Val 660 665 670 Val Asp Lys Asn
Gln Asn Thr Ser Glu Thr Leu Ile Glu Val Pro Asn 675 680 685 Phe Ala
Tyr Ile Pro His Val Glu Arg Ile Thr Gln Glu Gly Leu Ile 690 695 700
Ser Gly Val Ala Glu Asp Asn Ser Thr Val Ile Val Arg Asp Ala Asp 705
710 715 720 Gly Asn Glu Leu Gly Lys Val Thr Leu Gly Asp Asp Asn Ser
Trp Ser 725 730 735 Asp Phe Ser His Phe Ser Leu Ser Val Asn Arg Pro
Leu Ile Asp Gly 740 745 750 Glu Lys Ile Ser Val Gln Ile Ile Asp Asn
Lys Gly Leu Met Ser Pro 755 760 765 Glu Gln Asn Ile Ile Val Asp Leu
Thr Pro Pro Pro Ala Pro Thr Glu 770 775 780 Leu Asn Phe Asn Asp Ala
Gly Asp Leu Val Tyr Gly His Ala Glu Pro 785 790 795 800 Phe Ser Glu
Ile Leu Val Lys Asp Gly Gln Gly Asn Ile Leu Asn Lys 805 810 815 Trp
Phe Trp Asn Asn Trp Thr Asp Glu Ser Gly Ser Phe Ser Ile Glu 820 825
830 Leu Gly Thr Phe Leu Thr Asn Ala Glu Thr Val Tyr Val Thr Ala Thr
835 840 845 Asp Val Asn Gly Asn Val Ser Leu Ala Ala Gln Ile Gln Ala
Pro Asn 850 855 860 Tyr Ala Phe Ala Pro Tyr Val Asp Ser Phe Thr Ser
Asp Gly Val Ile 865 870 875 880 Ser Gly Gln Ala Glu Asn Asn Ser Thr
Leu Val Val Lys Asp Ala Lys 885 890 895 Gly Asp Val Val Ala Glu Ile
Lys Val Gly Glu Asp Asn Gly Trp Asn 900 905 910 Gly Ser Ser Tyr Phe
Lys Leu Gln Leu Asp Arg Pro Leu Val Asp Gly 915 920 925 Glu Gln Phe
Phe Leu Ser Ile Lys Asp Ala Arg Gly Gln Val Ser Ala 930 935 940 Asp
Thr Val Ile Thr Ala Asp Thr Val Ala Pro Thr Pro Ala Ser Asn 945 950
955 960 Leu Val Phe Ser Glu Asp Gly Ser Tyr Leu Thr Gly Val Ala Glu
Leu 965 970 975 Asn Thr Thr Ile Gln Val Phe Asp His Asn Gly Gln Leu
Val Asn Ile 980 985 990 Trp Asn Asn Thr Ile Asn Ser Asp Gly Thr Phe
Thr Ile Tyr Leu Gly 995 1000 1005 Ser Asn Asn Leu His Gly Glu Ala
Phe Thr Val Thr Val Lys Asp 1010 1015 1020 Gln Ala Gly Asn Val Ser
Glu Ala Ile Ser Ile Asn Ala Pro Leu 1025 1030 1035 Asp Asp Ile Ala
Pro Asn Pro Ile Lys Asn Ile Leu Leu Asp Ala 1040 1045 1050 Asn Gly
Gln Asn Phe Thr Ala Gln Ala Glu Ala Asn Ser Gln Ile 1055 1060 1065
Glu Val Phe Asp Ser Leu Gly Asn Gln Thr Gly Trp Gly Ser Thr 1070
1075 1080 Asp Ser Ala Gly Asn Val Ser Gly Ser Phe Asn Gln Thr Tyr
Leu 1085 1090 1095 His Gly Glu Glu Leu Thr Phe Val Val Ile Asp Arg
Ala Gly Asn 1100 1105 1110 Arg Ser Ile Glu Phe Lys Gln Asn Ala Leu
Ile Asp Thr Ile Ala 1115 1120 1125 Pro Asn Pro Ile Ala Asn Ile Ile
Phe Asn Glu Asp Gly Gln Ser 1130 1135 1140 Phe Thr Ala Gln Ala Glu
Ala Gly Ser Ser Ile Asp Val Leu Asp 1145 1150 1155 Gln Thr Gly Asn
Lys Ile Gly Phe Gly Tyr Thr Asp Ser Ser Gly 1160 1165 1170 Asn Val
Ser Gly Tyr Phe Gln Gln Val Tyr Leu His Gly Glu Glu 1175 1180 1185
Leu Thr Phe Val Val Ile Asp Arg Ala Gly Asn Arg Ser Ala Glu 1190
1195 1200 Val Lys Gln Ser Ala Leu Asn Asp Asp Val Val Pro Asn Pro
Ile 1205 1210 1215 Glu Asn Ile Val Leu Asp Leu Asn Gly Gln Asn Phe
Thr Ala Gln 1220 1225 1230 Ala Glu Ala Asn Ser Gln Ile Glu Ile Lys
Asn Asn Asn Gly Asp 1235 1240 1245 Val Val Gly Tyr Gly Ser Ala Asp
Ser Ala Gly Asn Val Ser Gly 1250 1255 1260 Tyr Leu Tyr Gln Val His
Leu His Gly Glu Glu Leu Thr Phe Ile 1265 1270 1275 Val Val Asp Arg
Ala Gly Asn Arg Ser Thr Glu Val Lys Gln Asn 1280 1285 1290 Ala Leu
Ile Asp Asp Ile Ala Pro Asn Pro Ile Glu Asn Ile Val 1295 1300 1305
Leu Asp Ile Asn Gly Gln Asn Phe Thr Ala Gln Ala Glu Ala Asn 1310
1315 1320 Thr Gln Ile Glu Val Lys Asn Ala Val Gly Glu Ile Val Gly
Leu 1325 1330 1335 Gly Tyr Val Asp Gly Ala Gly Asn Val Ser Gly Tyr
Leu Tyr Gln 1340 1345 1350 Val Tyr Leu His Gly Glu Glu Leu Thr Phe
Val Val Val Asp Arg 1355 1360 1365 Ala Gly Asn Arg Ser Thr Glu Val
Lys Gln Asn Ala Leu Ile Asp 1370 1375 1380 Asp Ile Ala Pro Asn Pro
Ile Glu Asn Ile Val Leu Asp Ile Asn 1385 1390 1395 Gly Gln Asn Phe
Thr Ala Gln Ala Glu Ala Asn Thr Gln Ile Glu 1400 1405 1410 Val Lys
Asn Ala Val Gly Glu Ile Val Gly Leu Gly Tyr Val Asp 1415 1420 1425
Gly Ala Gly Asn Val Ser Gly Tyr Leu Tyr Gln Val Tyr Leu His 1430
1435 1440 Gly Glu Glu Leu Thr Phe Val Val Val Asp Arg Ala Gly Asn
Arg 1445 1450 1455 Ser Thr Glu Val Lys Gln Asn Ala Leu Ile Asp Asp
Ile Ala Pro 1460 1465 1470 Asn Pro Ile Glu Asn Ile Leu Leu Asp Ala
Asn Gly Gln Asn Phe 1475 1480 1485 Thr Ala Gln Ala Glu Ala Asn Thr
Gln Ile Glu Val Lys Asn Thr 1490 1495 1500 Ala Gly Glu Val Ile Gly
Ser Gly Ser Thr Asp Ser Met Gly Asn 1505 1510 1515 Val Ser Gly Tyr
Phe Tyr Gln Val Tyr Leu His Gly Glu Glu Leu 1520 1525 1530 Thr Phe
Val Val Val Asp Arg Ala Gly Asn Arg Ser Thr Glu Val 1535 1540 1545
Lys Gln Asn Ala Leu Ile Asp Asp Ile Ala Pro Asn Ala Ile Glu 1550
1555 1560 Asn Ile Ile Phe Asn Glu Asn Gly Gln Asn Phe Thr Ala Gln
Ala 1565 1570 1575 Glu Ala Asn Ser Lys Val Glu Val Lys Asn Ala Ala
Gly Glu Val 1580 1585 1590 Val Gly Ser Gly Tyr Val Asp Ser Val Gly
Asn Val Ser Gly Tyr 1595 1600 1605 Leu Asn Gln Val Tyr Leu Lys Gly
Glu Glu Leu Thr Phe Val Val 1610 1615 1620 Ile Asp Gln Ala Gly Asn
Arg Ser Ile Glu Val Lys Gln Thr Ala 1625 1630 1635 Phe Leu Asp Asn
Thr Ala Pro Glu Asn Ala Thr Asn Leu Val Phe 1640 1645 1650 Ser Glu
Asp Gly Ser Tyr Leu Ser Gly Met Ala Glu Pro Asn Ala 1655 1660 1665
Thr Ile Gln Ile Phe Asp Gln Tyr Gly Gln Leu Leu Asn Gln Trp 1670
1675 1680 Asn Asn Asn Val Asn Trp Asp Gly Thr Phe Asn Ile Tyr Leu
Asn 1685 1690 1695 Ser Asn Tyr Met His Gly Glu Val Phe Lys Val Val
Val Val Asp 1700 1705 1710 His Ala Gly Asn Leu Ser Gly Glu Val Thr
Val Lys Ala Pro Leu 1715 1720 1725 Asp Asp Ile Ala Pro Val Ala Ala
Ser Asp Leu Val Phe Asn Glu 1730 1735 1740 Asp Gly Ser Ser Leu Ser
Gly Val Ala Glu Pro Asn Thr Phe Ile 1745 1750 1755 Gln Ile Phe Asp
Gln Asn Gly Gln Gln Met Asn Thr Trp Ser Gln 1760 1765 1770 Ser Val
Asn Ala Asp Gly Thr Phe Thr Ile Phe Phe Gly Thr Tyr 1775 1780 1785
Asn Leu His Gly Glu Glu Phe Thr Val Ile Val Lys Asp Leu Ala 1790
1795 1800 Gly Asn Val Ser Glu Ala Val Ser Val Lys Ala Pro Leu Asp
Asp 1805 1810 1815 Ile Ala Pro Lys Pro Ile Lys Asn Ile Val Phe Asp
Ala Asn Gly 1820 1825 1830 Gln Ser Phe Thr Ala Gln Ala Glu Ala Asn
Ser Gln Ile Glu Ile 1835 1840 1845 Phe Asp Ser Phe Gly Ser Gln Ile
Gly Trp Gly Ser Thr Asp Ser 1850 1855 1860 Thr Gly Ser Val Thr Gly
Tyr Phe Tyr Gln Val Tyr Leu His Gly 1865 1870 1875 Glu Glu Leu Thr
Phe Val Val Ile Asp Arg Val Gly Asn Arg Ser 1880 1885 1890 Asp Glu
Met Lys Leu Asn Ala Leu Met Asp Thr Ile Ala Pro Lys 1895 1900 1905
Pro Ile Glu Asn Ile Ile Phe Asn Glu Asn Gly Gln Asn Phe Thr 1910
1915 1920 Ala Gln Ala Glu Ala Asn Ser Phe Ile Ser Val Lys Asn Ala
Ala 1925 1930 1935 Gly Glu Phe Val Gly Tyr Gly Tyr Val Asp Ser Thr
Gly Asn Val 1940 1945 1950 Ser Gly His Phe Asn Gln Val Tyr Leu Lys
Gly Glu Glu Leu Thr 1955 1960 1965 Phe Ile Val Ile Asp Lys Ala Gly
Asn Gln Ser Ile Glu Tyr Lys 1970 1975 1980 Gln Asn Ala Leu Thr Asp
Asp Ile Ala Pro Asn Pro Ile Glu Asn 1985 1990 1995 Ile Val Leu Asn
Lys Asn Gly Gln Asn Phe Thr Ala Gln Ala Glu 2000 2005 2010 Ala Asp
Ser Gln Ile Glu Val Lys Asn Thr Ala Gly Glu Val Val 2015 2020 2025
Gly Ser Gly Tyr Val Asp Ser Ile Gly Asn Val Ser Gly Ser Phe 2030
2035 2040 Asn Gln Val Tyr Leu His Gly Glu Glu Leu Thr Phe Val Val
Val 2045 2050 2055 Asp Arg Ala Gly Asn Arg Ser Thr Glu Val Lys Gln
Asn Ala Leu 2060 2065 2070 Ile Asp Asp Ile Ala Pro Asn Gln Ile Glu
Asn Ile Val Phe Asp 2075 2080 2085 Val Asn Gly Gln Tyr Phe Thr Gly
His Ala Glu Ala Asp Thr Arg 2090 2095 2100 Ile Glu Val Leu Asp Gln
Phe Gly Asn Arg Ala Gly Trp Gly Tyr 2105 2110 2115 Val Asp Ser Gln
Gly Asn Val Ile Gly Tyr Phe Asn Gln Val Tyr 2120 2125 2130 Leu His
Gly Glu Glu Leu Thr Phe Ile Val Val Asp Ile Ala Gly 2135 2140 2145
Asn Arg Ser Val Glu Val Lys Gln Asn Ala Leu Ile Asp Asn Val 2150
2155 2160 Ala Pro Pro Ala Ala Ala Asn Ile Thr Leu Thr Ser Asp Gly
Leu 2165 2170 2175 Leu Phe Gly Glu Ala Glu Pro Asn Ser Thr Val Glu
Ile Ile Asp 2180 2185 2190 Gln Tyr Gly Ala Val Ile Thr Thr Thr Tyr
Val Trp Tyr Asp Gly 2195 2200 2205 Thr Phe Asn Gln Trp Ile Asn Leu
Ser Gln Tyr Gln Thr Gln Asn 2210 2215 2220 Leu Ser Ile Val Val Lys
Asp Gln Ala Gly Asn Arg Ser Glu Val 2225 2230 2235 Val His Glu Leu
Val Pro Val Phe Thr Asn Ser Pro Ile Ala Ala 2240 2245 2250 Thr Glu
Leu Lys Leu Asp Ile Asp Gly His Ile Leu Thr Gly Lys 2255 2260 2265
Ala Thr Val Gly Met Ser Val Val Val Thr Ser Thr Asp Gly Gln 2270
2275 2280 Thr Ile Asn Gly Gly Trp Asn Asn Ala Val Asn Glu Asp Gly
Ser 2285 2290 2295 Phe Ala Ile Gln Leu Asn Asp Tyr Tyr Leu Gln Gly
Gln Thr Leu 2300 2305 2310 Gln Val Arg Val Tyr Asp Gln Asn Thr Asn
Gln Tyr Ser Leu Ile 2315 2320 2325 Ser Glu Ile Ile Ala Pro Leu Asp
Asn Ile Ala Pro Val Ile Asn 2330 2335 2340 Glu Val Val Ile Asn Asn
Asp Gly Tyr Gly Ile Thr Gly Gln Thr 2345 2350 2355 Asp Ser Lys Ala
Ile Ile Gln Val Met Asp Ala Asp Gly Asp Leu 2360 2365 2370 Arg Ala
Glu Phe Gln Ala Asp Glu Thr Gly Tyr Phe Asn Ala Ser 2375 2380 2385
Ile Tyr Pro Pro Ile Leu Arg Gly Glu Gln Leu Phe Ile Thr Ala 2390
2395 2400 Ile Asp Leu Ala Lys Asn Ile Ser Lys Pro Phe Asn Ile Thr
Phe 2405 2410 2415 Asn Ala Asp Thr Asn Ala Pro Pro Ser Ala Glu His
Ile Val Val 2420 2425 2430 Ser Glu Asn Gly Phe Phe Ile Glu Gly Thr
Ala Val Ala Ile Ser 2435 2440 2445 Thr Val His Ile Phe Asp Val His
Ser Asn His Val Ala Thr Asn 2450 2455 2460 Val Ala Asp Glu Ala Gly
Asn Phe Asn Ile Gln Leu Tyr Pro Pro 2465 2470 2475 Leu Ala Ser Gly
Gln Ile Leu Arg Ile Val Val Glu Tyr Asn Gly 2480 2485 2490 Tyr Gln
Ser Ala Tyr Thr Glu Ile Thr Ala Pro Ile Asp Thr Val 2495 2500 2505
Ala Pro Asn Ala Ala Thr Gln Leu Leu Leu Glu Asp Gly Asn Val 2510
2515 2520 Leu Ser Gly Gln Ala Glu Ala Tyr Ser Ile Val Asn Ile Phe
Asp 2525 2530 2535 Ala Asn Asn Asn Leu Val Gly Gln Thr Asn Val Gly
Ser Asp Gly 2540 2545 2550 Ala Phe Leu Thr His Leu Trp Tyr Glu Tyr
Trp His Gly Glu Thr 2555
2560 2565 Leu Thr Val Lys Val Val Asp Ala Asn Gln Asn Val Ser Val
Gly 2570 2575 2580 Thr Thr Ile Val Ala Ile Asn Asp Thr Val Val Pro
Asp Val Val 2585 2590 2595 Thr Gln Leu Ala Ile Asp Glu Trp Gly Ser
Leu Thr Gly Arg Val 2600 2605 2610 Glu Ser Tyr Ala Thr Val Glu Leu
Thr Tyr His Phe Thr Asp Gln 2615 2620 2625 Pro Leu Ser Val Thr Ser
Thr Thr Ala Leu Ala Asn Gly Met Phe 2630 2635 2640 Phe Ile Tyr Leu
Asp Arg Asn Ala Thr Ser Leu Asp Leu Thr Val 2645 2650 2655 Ile Asp
Arg Ala Gly Asn Arg Ser Glu Thr Ile Ser Gln Ile Ile 2660 2665 2670
Ser Asp Leu Pro Thr Val Ile Ile Asp His Phe Lys Gly Asp Ala 2675
2680 2685 Thr Asp Asn Thr Tyr Asn Ile Asp Thr Ile Asp Asp Phe Val
Gln 2690 2695 2700 Glu Tyr Ile Val Glu Pro Tyr Ala Ile Tyr Lys Asp
Val Trp Ile 2705 2710 2715 Asp Asn Ser Tyr Met Tyr Ser Asp Trp Val
Ile Glu Gly His Tyr 2720 2725 2730 Glu Gln Ile Trp Phe Val Asp Gly
Tyr Tyr Glu Ser Gln Trp Ala 2735 2740 2745 Thr Ser Gly Tyr Ser Thr
Val Gln Asn Ile Tyr Gln Asn Gln Asn 2750 2755 2760 Gly Ile Thr Tyr
Ile Asp Asn Gly Thr Ala Asp Ser Asp Tyr Ser 2765 2770 2775 Arg Tyr
Glu Gln Gln Tyr Tyr Asp Phe Val Asn Gly Gln Trp Gln 2780 2785 2790
Glu Gly Tyr Glu Leu Thr Tyr Ile Arg Ser Glu Glu Gly Trp Val 2795
2800 2805 Asp Thr Ser His Tyr Glu Asp Val Tyr Ile Asp Thr Ser His
Tyr 2810 2815 2820 Glu Glu Val Trp Val Asp Thr Ser His Tyr Gln Asp
Ile Trp Val 2825 2830 2835 Glu Asn Ser Tyr Trp Glu Ser Gln Leu Val
Glu Ser Gly Arg Arg 2840 2845 2850 Asp Val Asp Leu Gly Gly His Asp
Lys Ile Ile Ser Ser Val Asn 2855 2860 2865 Tyr Ser Leu Val Gly Leu
Tyr Gln Thr Val Asn Asp Pro Thr Thr 2870 2875 2880 Val Asp Ser Phe
Leu Glu Ser Gly Arg Tyr Val Glu Asp Leu Glu 2885 2890 2895 Leu Val
Gly Ser Ala His Leu Asn Ala Thr Gly Asn Ala Leu Asp 2900 2905 2910
Asn Leu Leu Thr Gly Asn Ser Gly Asn Asn Val Leu Asn Gly Arg 2915
2920 2925 Glu Gly Asn Asp Thr Tyr Ile Thr Asn Glu Gly Thr Asp Thr
Ile 2930 2935 2940 Val Phe Gln Leu Leu Asn Ser Gln Asp Ala Thr Gly
Gly Asn Gly 2945 2950 2955 His Asp Thr Val Leu Asp Phe Thr Leu Gly
Asp Ile Arg Thr Asn 2960 2965 2970 Leu Gln Ala Asp Lys Ile Asp Leu
Ser Glu Leu Leu Ile Asp Tyr 2975 2980 2985 Ser Lys Asp Val Ser Ala
Leu Ala Lys Phe Ile Thr Val Glu Gln 2990 2995 3000 Asp Ala Gly Asn
Thr Thr Ile Ser Leu Asp Arg Asp Gly Glu Gly 3005 3010 3015 Thr Met
Phe Asn Ser Val Ser Leu Leu Thr Leu Asn Gln Val Asn 3020 3025 3030
Thr Thr Leu Asp Glu Leu Leu Asn Asn Gln Gln Ile Ile Val 3035 3040
3045 31183DNAAcinetobacter baumannii 31atgacacagc tcattaataa
aggtggcttt cgtgaaagag ccaatagaag ccgaaaatat 60caacaatctg aaaacaagca
agtagctctg ccttcaaaaa agtatcaacc tcaaactaaa 120ctccaagata
atcaaagcga gatgattcaa gcaaaagcag gtactgctga aacttcagat 180taa
18332201DNAAcinetobacter baumannii 32atgaaattag ctaaaacttt
actcgctact accctagctt taactgctgc ttcaactttc 60gctgcttcta agcacgacca
agcacataac actgctggtg aagaaaaagt tgttgtttca 120actcaagagc
aagcaaacac tgcaaatgct gcttctgacg ctgtaggttc tgcttctgaa
180gctgctcctg caactcgtta a 20133201DNAAcinetobacter baumannii
33atgatagatg aagaaaagcc tttaaatttt gaagatgatg acgagcctct tgattttgaa
60gatgaagaat tcatagacga taaaaaagag gacgaaatgt ataactcgat tactaaggat
120ggctctagtg tcgatcctgc tgatgatggg acacgacata ttcgtcctga
agacggcgat 180ccgattgaaa ttgatgagta a 20134222DNAAcinetobacter
baumannii 34atgagcacta ctaataatca agcaaatcaa cgcaataatc agcagcaaca
acaacagcaa 60aatgacaacc gtaatcaaca gcaacacggt aaccaacagc aaaacgatca
acagcaacaa 120aataaccagc aacaacagca aaatgataac cgcggtcaac
aacaaggatc taatcaaaaa 180gattctggcc aacaaaactc aaataacaac
caacaacgtt aa 22235327DNAAcinetobacter baumannii 35atgtcagcaa
aactagttgt tactttgtta gcaaccagtc ttttaactgt aggctgtgtt 60gcttatacag
atgatcctta ttatcgcggt ggttatggtt accatgatca tgacgacgat
120cgttatgacc gtaacgatgg acgtcgatat agtgagtggg aacgcaaacg
ttgggaagag 180cgtaaaagat tatatgaaca acaacgcaaa gatattcgtg
aacagcaaaa ggatcgtcgt 240gaatgggaaa aacgacaccg tgaatgggag
aagaaacgct tagaagaccg agatcatgat 300catagagatt atcgtcatga tgactaa
32736345DNAAcinetobacter baumannii 36atgaataaat tacttgttgc
tttaggtctt gctgcgactg ttgcccttgt tggttgtaat 60aaagataaag ctccagaaac
tggtgctact acaggtgaac acttagaaaa tgctgctcaa 120caagcaacag
cagatatcaa atctgctggt gatcaagctg cgagcgatat tgcaactgca
180acagacaacg cttcagctaa aattgatgct gctgctgacc atgctgctga
tgcgactgct 240aaagctgcag ctgaaacaga agctactgca cgtaaagcga
ctgctgatac agctcaagct 300gttgaaaatg cagctgctga tgtgaaaaaa
gatgctcaac actaa 34537381DNAAcinetobacter baumannii 37atgaaaatga
cggctaaaat tgcattattc agtgcagcaa ttgtaactat gggtagtttg 60gctgcttgtc
aatcaacaac tcaaccacct aagccagaac atggcatgat gcaagatggc
120ccacgtgatg gtcaccacca tcgtatgaaa caccgtgaat ttacgcctga
acaaaaagca 180gcatgggaac aacaccgtgc agagcgtaaa gctcgttttg
agcaaattca aaaagcatgt 240gaaggtaaag ttgttggaca aactgtcaat
gttcaagttg gagataaaac acttgaaggt 300acatgtaacc tccgctttga
gccaaaacgt cctcaaccac cagtcaatgc ccctgctcca 360gtagcgactc
aagcaaaata a 38138420DNAAcinetobacter baumannii 38atgaaagcca
taaaaatttt atgtattaca agctctatct tggtttcatc atctctcttt 60gctgaaacac
ctcaacctca acaagtgaat gaagcaactt ctaagacaat gccttatggt
120gataatccaa gcttaggccg cgtactgtta tacaaaacag gaaaaggcat
tcaaaattta 180ggagattcta ttcaaggcgc ttctgaaaaa acttcaaata
aaattagtga aaaatggaaa 240gatacgaaag aatttaccgc cgaaaaagca
gaagttgttc aacaaaaagc ggatacagcc 300aaagtattta ctgaacagaa
aatagaacaa gctaagcaaa atatcaccag cagtagaaac 360ggtgaaaata
ttccaatcga acaaggtgag ctaagtaaat ctagtacgac tgccaattaa
42039480DNAAcinetobacter baumannii 39atgaaaaaat cattattagc
aattgcactt atgagtactc ttcttgtcgc atgtaataaa 60catgaaaata aaacagaaac
aacctctgat gcatctactc ctgtacaaac tgctcaatca 120aataataatg
aagcggtaga tacagcacat acagccgaga attctttaga ttgggatggt
180aaatataaag gtacgcttcc ttgtgcagac tgtgaaggca tcaaaactga
attagagtta 240aaagatgata aaacttatga gctaacagaa acctatcttg
gtaaaggtga tgcaaaccca 300tttgaaaccc atggtaagtt tactttcgat
aaagacaata cttctgttat taccttagat 360gataaagctc aaaaccgtaa
attctttatt ggtgaaaata cagcgacagc tttagatatg 420gaaggtaaaa
aagttgaagg ttctttagct gaacattatg ttttgaaaaa agaagattaa
48040489DNAAcinetobacter baumannii 40atggcaaata aaaaactttt
aatctgtgct gcaattgcgg ctggactatt gttaaccgca 60tgcgttaaaa aagagacacc
gaaagaagaa gagcaagaca aggttgaaac tgctgtttca 120gaacctcaac
cacagaagcc tgcaaaattt gaatctttag agagtgtaga tactcaagaa
180gctcaagttc aagagcaacc acaagttgaa gttcatcgtg aagaaactgc
taacacgaca 240actgaaattc gccgtgaaac tcgtcctgcg cgttctgatg
aatcttcaca gacacaagtt 300gctgaacaac ctaaatctga gacaccaaaa
gtagaaccta aaccagaaaa aaaacctgag 360cctaaagctg aacctaaacc
ggaaaaagct cagtcaaaac cagctgctaa ggcaactgag 420cctgcgaaca
cagaagatga tgccgttgct gctgctattg ctgctgcaac accagcactt 480aagaactaa
48941501DNAAcinetobacter baumannii 41atgactactg aaaataaatt
agatgaatta aaggcaaacg cggctgatgc aaaagtacaa 60ggtgaaaaag ctttggacga
tttaaaagaa aatgtaaaag agaaacaaac tgcgggtaaa 120gaagcaattg
cagataaagt agatgagcta aagaccaaag cggccgatgc aaaagtacaa
180ggtgaaaaag ccttggaaga tttaaaggaa aatgtaaaag aaaaacaagc
tgctgcaaaa 240gaggcagttg aagataaagc tagtgatttg aaaggcaaac
ttgatgatgc tcagcatagc 300ctgcaagaca agtttgatca tttacgtact
gaagcagcgc ataaacttga tgatgctaaa 360gccaaagctg cagaattaaa
ggaagaggcg gctacaaaat ttgatgagtt aaaaactcaa 420gcaactgcga
aatttgatga gttgaagaaa acagctaccg aaaaacttaa taaattgaaa
480aatcatgatt ctgctgaata a 50142693DNAAcinetobacter baumannii
42atgcacacgc gtcgtatttt attagcgttt tcacttgccg cttcggcagc atcggttgct
60tttgcagatt atcaaaatat taaccaatct actgattcag atcgattgga acagttatca
120aaaacactat ctcaaggctc atatactcat cctgatgatt tagatcttcc
ggcgagtgca 180aaagtttcag tgactttacg tgagaaaaca gttgaactca
acaatgattc actggcaaag 240aaatacggca caacgacagc taaaaactca
tttaaaacct cttcttcaaa tccttattct 300tggttagttt ctcatcctct
tcctgataca gtacgtgttt cttctaactt tggtggtcgt 360accatgggtg
gtcgtgcaga gcatcatggt ggtttagata tggctgcacc aagtggtacg
420ccaatctatg ccactggtcc gggtattgtg actaaatcag gctggggcac
aggttatggc 480caatatgttg aaattaacca tggtaatggt tatttaacac
gttatgcgca tgcttcacgc 540ttaatggttc gggtaggtga tcaggtttct
gcgggtgacc atattgctaa tgttggttgt 600acaggccgct gtactggtcc
acatttacat tacgaagtag ttaaagatgg tcaacgtaag 660aatccatcaa
cttacttagc aatgttgcct taa 69343717DNAAcinetobacter baumannii
43atgggcatga cttttacaga catagaaaat aaatctgcca aacgcctaat tggtattgct
60gcagtcattt ttctgcatct tcttgttgcc tatattctga tgtcaggttt agcaaacaat
120attcaaaaac cagcagaaaa acctgtggaa ttacaaatta ttcaggatat
taagccacct 180cctccaccaa agccggaaga gccgaaacca aaggaaaaac
cacctgagcc accaaaaatg 240gtagaaaaag ttgccaaggt tcctgagcca
ccaaaagaag tagagaaagt agcaacacca 300gtacaaaaaa cgacgccagt
agctcaaacg actaaagtcg ctactccggc tcctgctgca 360cctagtactc
cttctccgag ccctgttgct gcaccagctc cagtggcagc tgctgcacca
420gcacttaaac ccgctggtgt aactcgtggt gtttcagaag gctctgcggg
ctgcgaaaaa 480ccagaatatc cacgcgaagc actcatgaac gaagagcaag
gtacggtgcg tatacgtgtt 540ttagttgata cttccggcaa agtcattgat
gccaaagtaa aaaaatcgag tggtagcaaa 600accttagata aagcagcaac
taaagcctac agcttatgta cgttcaaacc agcaatgaaa 660gatggcgtac
ctcagcaaga ctggtatgaa attgaatatc cattcgtaat tgaataa
71744762DNAAcinetobacter baumannii 44atgaaaatga tgaaaacagc
tatcgttact gcaagtgtac ttgcttctgc ctctattttt 60gcacaaagtg cgggcgttaa
tgcaggtgca tctgctcaag tcaacgtaca accaggtggt 120cttgttagtg
gcgtagccaa tacagtcaaa aatactgcac atactgtagg gaacacagca
180aaacatgctg gtcacgtagc tgctgacaca accgttaaag ctacaaaaaa
aacaacaggt 240aaagtaactg aactttcttc taaagctgct actggtacta
aacatgtagc aagtgaagct 300gtaactggta ctaaacattt tgctaccgaa
gcagcaacag gtacaaaaaa tttagcgact 360aaggctgcaa ctggcactaa
aaacctagca gttgaagcta aagcagatac aaaagcacat 420cttgatgctg
taaaaactaa ggtagcagaa aaacaagctg accaaaaaga atttactgct
480gaaaaacagg ccgatgctca agcacgtgta gatgctgtta aagctcgtgt
agcacaaaat 540caagctgagc aaaaagaatt cgttgctgac actaaagctg
atgctcaagc aaaattaaat 600acagctcaac cagctcatgg agttaacgct
caaacaggtg taaacgttgg tgttaatgtt 660gctggtatta atgcaaatgc
aaacgtaaat gcaggcgctc aagcgtctac acaaaaaggc 720gaaaagaaat
cttttattaa aggtcttttc ggtactaact aa 76245885DNAAcinetobacter
baumannii 45atgcaaatga agaagcattc tttattattt attgccttaa tgagcaccac
ttctctatac 60gcaaatatcc ctatcgagtc tcgtggttta agtcaaaatg atggtagtgc
atctaatact 120tcttcaagca atatttcagt tcctacaaat ttaaactggg
aactcatgca aaaaaaccaa 180caattagaaa atgatattcg tacattaaga
ggtcagcttg aagaacaagc taatgatatt 240gagcaattaa agaaagatct
agcaaaccga tataccgact tagatcaacg tttagaatta 300ttacaccaaa
aagttgaccc tgacagtgct acacaagatg atagttcgaa tgcaacgtcc
360gataacacta ctcctgctag tgcaccagcc cctcaaacca cggagagtaa
taaagtagct 420gccgtaccag ccacacaaac ttctgagcag cagcctagcg
caccaacaac cactactcaa 480ccagcaccag ctgctgcgca aaaccagtca
aattccctcg aattagaaaa agctgcttat 540actgtagctt tagatgcgta
taaacaaggc ggtgctaaaa aagcaattgc tccaatgcaa 600aactttataa
aaaaccatcc taatagtatc tatacaggta atgcttattt ttggttagcc
660gagtttcatt tagcgacaga tccagtaaat tataatgaag caaagaaaaa
ctataatgtc 720gtagctaacc aatacccaaa ttcaagtaag gcacctcgag
cattgtacca actttatagt 780atcgctaaag atgttgataa gaatactgtg
tcagcaaatc aatacaagaa caagttactt 840agccaatatc caaaatctga
agaagcaaaa ttctttaaca aataa 885461071DNAAcinetobacter baumannii
46atgtcaatga ataacaaaca acgctggatg ggtggcgttg ttttattagg tggtggtgtt
60ttattggcag cattacttct aaaaggaaat gaagaaataa aacaggtaga tgttcaaccc
120caaacttcaa catcaccgaa attacaagct aagccaaagc aatcagcaca
agaagggcag 180atggtacagc tacagccact tgcagttgat gttgaaacag
aaaaacgtct tcttgaagaa 240cagcgccgtt ctcgtgaaaa agctgtagca
gaacaagagg ctcgtgctgc cgaattcttg 300gcaatgcaac aacaggcaga
agcggatgca gctcgtaaag ctgctgctga atatgccgcg 360attaatgctc
gccgagctgc tgcacaagaa agttccgata atattcctcc tgaagtcgcg
420ggtagtgaga ataaggcaaa aggacagcaa actgatacaa aaaagtcagt
agatctggct 480aaagcggatg cagataaaaa agctgctgaa gcgaaacgct
tagctgaggc ggataagaaa 540gcggctgagg caaaacgtca ggcagaagca
gacaagaaag cagcagaggc taaacgccaa 600gcagaagcag ataagaaagc
agctgaggca aaacgtcagg cagaagcgga taagaaagca 660gcagaggcga
agcgccaagc agaagcggac aaaaaggctg ctgaagctaa acgtcaagca
720gaagcagata agaaagcagc tgaagcgaaa cgtaaggcag aggccgagaa
aaaagctgaa 780gcagagaaag cacgtgagtt gcttgaaaat ggtgataaaa
aatggatggt acaggttgca 840ttggctgcta accaagcaaa tgcagatgct
gtagtctcta aattacgtgc aaaaggctat 900aaggtcacga cgagtccaac
cagtaaaggt atccgtatta tggttggtcc tgcaaaagat 960agagatacgg
cagatactac acgtaagaaa attacttctg acgccagttt aaatatgaag
1020tcagcttggg tgattgactg ggtgccttta gatcagcgta agtcagatta a
1071471104DNAAcinetobacter baumannii 47atggctaata ctagatatga
agatgataac aatagttcag gtacttcaaa tcgtggattt 60gcaagtatgg atcctgaaag
agtcagagaa atagccagta aaggtgggcg agctgcacat 120gccagtggca
atgcgcatga atttacttca gaagaagctc gtgaagctgg ccgtgctgca
180catgccagtg gtaacgcaca tgaatttacc tcagaagagg ctcgtgaagc
tggtgcttta 240agtcataaaa acgatgatcg taatggtcgt ggtcgcagcc
gttatgatga cgacgaagat 300gatgaccgcg gccgttcaag tggtcgaggc
cgtggccgca gtcgttatga tgatgacgac 360gaagatgatg atcgcggtcg
ctcaggcggt cgtggccgtg gtcgcggtcg tgatgatgac 420gacgaagatg
atgatcgcgg tcgctcaggt ggccgaggcc gtggtcgcag tcgtgatgat
480gacgatgaag atgatgatcg cggtcgttca ggtggccgag gtcgtggtcg
cagccgccgt 540gatgatgacg atgaagatga tgatcgcggt cgttcaggcg
gtcgaggtcg tggccgcagc 600cgtcgtgatg acgacgatga agatgatgat
cgcggtcgct caggtggccg aggtcgtggt 660cgcagccgtt atgatgacga
cgatgaagat gatgaccgtg gccgttcagg cggtcgaggt 720cgtggccgca
gccgtcgtga cgatgatgac gaagatgatg atcgtggtcg ttcaggtggc
780cgaggccgtg gccgcagtcg ttatgatgac gacgatgaag atgatgatcg
tggccgttca 840ggtggccgag gtcgtggccg cagccgtcgt gatgatgacg
atgaagatga tgatcgcggt 900cgttcaggtg gtcgaggccg tggccgcagt
cgttatgatg atgacgatga agatgatgat 960cgtggtcgtt caggtggccg
aggccgtggt cgcagccgtc gtgatgacga tgacgacgat 1020gatgaccgcc
gtggccgttc agacggtcgt ggtcagaact ctcgtaatca aaaacgcgat
1080gcttatggac gctttacgtc ttaa 1104481263DNAAcinetobacter baumannii
48atgttatatg tgattccgtt tatcatatta ctcgtggtcg ccgttatttt aaaaaaacgc
60gagaatagtc aaaaacaaga ggccacttcc ccaaaaaata taaatagaaa atccggcaaa
120aaagcgagtg ctaaatcaag caaaagctcg cgtgaaaaaa taaaagccaa
ggtcattgag 180gaaaatattc ctgctatccc tcaaagtaat cctgtaccgg
aagctttacg acacaatatt 240caacagctca ttcaagaaaa acagttttca
gcagctgaag ctcaagtcaa tcaggcgcta 300aaaaaagata atactcaaca
tgaactgtat ttattacttc ttgaaattca tattgctcag 360aaagatgaat
ttgcaattca acagttgatt agccatattc gtagcttggg tttaaatgaa
420atagcagctc aagcagaaac tcgacaaaaa gaatatgaat catccagcca
acctgatgct 480attgatttcc ctcaagctca aacatatgaa gaaccgaaaa
acacagatac aacggctcag 540ttcgatgaat taacaacaag ttcttccgag
gcttcttttg atgacctaca gaaagactat 600acccctgtaa aacaagaacc
tgctattgaa attgaacctt tagagtttaa cttttcattc 660gaacagaatt
cggctacgga aaataccaac caaccagcac aacaacctga gttatcatcc
720actcaagaaa caaatgagct ggccgattta gagttttctt ttgacttggc
ccctctgcat 780gaaactgagg aaaaatctca agcagtagag gtaaaagcag
accaagaaaa tagcatcaat 840gcattagatt ttaactttga cttaaatcct
tcaagttcag agacgaaatc tgttcaacaa 900gctccctcat tagatgaaat
taagctcata gaacaagccc cattagaagc gacttctatc 960gcacctcttg
agttttcgtt agatgagcct gccttagttc cagcaccaga gcttgaaact
1020caaaaccata tagatgtagt aaatgaagca gccactcaaa cccaaataga
ggatccgctt 1080ttagaagctt ttccagaatt aaaacaaata aatgaaaatg
aactcgattt aaaattggct 1140gaacaataca ttaagtttgg cgcaaaccaa
gcagcgcgta atttactaca gggtgatgag 1200caaaaattca acacagaaca
acaacaacat gcgaaaaacc tacttaatcg catagcttct 1260tag
1263491338DNAAcinetobacter baumannii 49atgccaaaaa taaagccaat
taaactcgta attattgtcg tctgtatcgc cattattgct 60gtcttagctt ggaaattctt
aaagcctaaa caacagcaac ctcaatatat tacagcagag 120gtaactcgtg
gggatattga gaataatgta cttgcaaccg gtacacttga tgcaaccaag
180ctcattagtg tgggtgctca ggtatctggt caggttaaaa agatgtatgt
gcagcttggt 240gatcaagtaa aacaaggtca acttattgca caaattgact
cgaccaccca agaaaacagt 300ttaaaaacat ctgatgctaa tattaaaaat
ttagaggcac agcgtcttca gcaaatcgct 360tctttaaacg agaaacaact
cgaatatcgt cgtcaacaac aaatgtatgc tcaagatgca
420acacctcgtg cagatttaga gtcggctgaa gctgcttata aaacagctca
ggcacaagtt 480aaagcattag atgcacaaat tgagtctgca aaaataacgc
gttcaacagc acaaaccaat 540attggctata cccgtattgt tgcgccaact
gatggtacgg ttgttgcgat tgtgactgaa 600gaaggtcaaa cggtaaacgc
aaaccaaagt gctcctacta tcgtcaaaat tgcaaaactt 660caaaatatga
cgattaaagc acaggtgagt gaagccgata ttatgaaagt ggaaaaaggt
720cagcaggtct atttcacgac cttaggtgat gaaaccaagc gctatgcaac
cttacgtcaa 780atcgaacctg ctccagattc aatctctagt gaatcaaaca
gcaccacaag ttcaacaaca 840agctcagctg tttactacaa cgctttattt
gatgttccaa atacggacgg caaattgcgt 900attgatatga ctgcacaagt
ttatatcgta ttaaattcag caaaaaatgc cttattggtt 960ccatcttctg
cgttaagtag caaacaattt tctggccaaa gaaaacaggg gcaatcggca
1020gataaagcaa gttctactcc aagtgcagaa cgcaagcatc aaggtaacgg
cgtccgttta 1080gaacgcttaa atttaactcc tgaacaaaaa caacttattg
aacaaggcaa agcaactctg 1140agtgtagttc gcgttttaca agcagatggt
acgactaaac caacacaaat tttggtaggt 1200attaataacc gtgtaaatgc
acaagtactt gccggattaa aacaaggtga ccaagttgtg 1260attgctgata
gttcagaaaa ctctgcagct tctgcaaaca gtggtaataa ccgccgccgt
1320ggcccaatgg gaatgtaa 1338502136DNAAcinetobacter baumannii
50atgaatatcc cacctcgacc atttaagttg tctgtaatcg cctgcgcgat ttgttatgcc
60aacctcacct atgcccaaga tgcacaggta caagctttgc aaacgattca ggtcaaagca
120tcaaatgcag agcagtcttc tgaacagacc aaggcatata atgttaaaaa
ctcaagtagt 180gcaaccaagc ttaatattga ggctaaggaa acaccccaaa
ccattaatgt cgttactcgt 240cagcaaattg aagattttgg ccttaccagt
actcgtgatg ttttaagaaa tacccctggt 300gtaacagtct ctaatcaaga
aactgagcga accacttata tggctcgtgg ttttgagatt 360tcaaatatct
tgacggatgg cgtaggcttt cctctttcag gttataacta taataatacg
420aatcctgata cttactttta tgatcgtgta gaagtagtta aaggagctga
ctcgttaact 480aatgcctttg gcgatccgag tgcaaccatc aataatattc
gaaaacgtcc aacccaagaa 540tttcaagcaa gcggtggtgt aagttacggt
tcatgggata cgcagcgcta tgaagctgac 600gtatctggct caattctacc
aagtggaaaa gtacgtggcc gtattatggg ctatgaacaa 660actggtgatt
cttacctaga ccgatattct gcggaaaaaa acggctttgc tggtattgtt
720gaagccgatt taacagatag cactttactt accgcaggtt atagccaaga
acaaaataaa 780cccaatgcaa acaactgggg tgcactacct ttattagatg
ccaacggtaa acaaatttcc 840tatgaccgct catataatcc aaaccctgat
tgggcacatt gggataatga gacacaaaat 900gcttttgttg aattaaagca
aaaacttaat gaccaatgga atgctaaact gacttacaac 960tatcttgata
cgaagcataa tagccgtctt ctctattact atggttaccc aaaagctgat
1020gggtccggtg tttctctaac gccttggggt ggacaagaac atcaagaaaa
acatgctgta 1080gattttaatc tcgaagggac ctataagcta tttaaccgag
aacatgaagc aactctaggc 1140tacagctatg tacgtaatca tcaacaagat
aaacaatcta caggaacgat taacgatagt 1200aacgttataa agtcaactac
gaccgattgg gcaagttgga caccgcaatc tataacttgg 1260tcagatttca
cagaagcggc taactataaa caaaatatta actcaattta tgccgcgaca
1320cgtttacatc ttaatgaaga tttaaaactt ttacttggtg caaactatgt
tcaagctgag 1380agtaaaggcg aaagttatag ctcaccaatg tcatatagtg
aaagtaaagt ttctccatat 1440gtcggattaa cctataattt tacacctgaa
tatacgggtt acatgagtta tacctctatt 1500ttccgtccac aaactggtat
tgataaagat accaatcaag ctttaaaacc tattgagggt 1560aaaagctatg
aaatgggtgt aaaaagctca tggctagatg accgtttaac aggcacactt
1620tcagtattta aaactgaaca aaacaattac cctttacgta actcggatgg
aaacccactt 1680aaccgaaaag taccaacgag tgatctagaa tcgcaaggtg
tagaagtcgg tctatcaggt 1740caaattactg ataacgtaaa tctttctttc
ggctatgctc aatttagtat taaagacact 1800aaaaatggtg gcgaagcaag
aacatacaat ccaaaccaga cacttaactt gctaactacc 1860tatactccgc
cagttttacc taagcttaaa gttggtgcag gtttacagtg gcaagatggg
1920ataaagttat atgactcaaa tgtaaacggt acgatcaaac aagatgcata
tgctttagtc 1980aatttaatgg caagctatga agtcaatgat catattacgc
ttcaagcaaa tggtaataat 2040atttttgaca agaaatattt aaatagtttc
ccagatgggc aggcttttta tggtgcccca 2100gccaactata cagttgctgt
aaagtttaaa tattaa 2136512184DNAAcinetobacter baumannii 51atgaaacttc
aaactatagc ttgtgcagta gcaatcgcga ctggcggttt attcttctct 60catacgatga
acgaagcaag agcagcaacc aatactgctg ctgtttctca atcgatccag
120ccaacgcaag agcaagcctt ggtggctcgt caactggcaa ctttagtaga
ccgccaacat 180tatttaaata tgcgtctgga tgcgaacaca tctaaccgta
ttcttgatat gtacttagac 240agtcttgatc cggaccactc attattttta
gacgctgaag ttcaaaacta taaaaagctc 300tatggttcaa attttggtgc
ttcattaaaa gcggggaatt taactgggcc atttgctatt 360caccagcaat
atcgtgagcg cttaaagcag ttttatgagt tcatgcttgc tgagttgaag
420aaaccacaaa acttaaaaca gccaaatact tttattgaag tagatcgcga
aaaagcaccg 480tattttaaaa cgtcagctga acagcaaaat cactggcgta
aaatgctggt ttctcagtta 540attaatttaa cgattagccg tgaagaagag
caggcgaaac aaaaggcgtt aaaagaaaac 600ccttcacttg ctgatggtca
agacttaaca ggcccagaag atttaacgcc agctcagact 660ttgactaagc
gttatacgcg tcagcttgaa agaattagtc gtgtgaaaag cgacgatgtg
720ttggataaaa cattaaatgc aatgttggca acttatgatc cgcacagtaa
ctattatccg 780ccaattgatg cgatagaact gaaccgccaa acaaccttac
agcttgaagg tattggggta 840tcgattcgcc cagaacgtgg taatgaagat
tacaccaaga ttgaaactat tgtagaaggt 900ggtcctgcaa gtaagtctgg
tcaagtgaaa tcaggagacc gaatcgttgg tgtcgctcaa 960gagggcggca
aaatgatcga tgtggtcggc tggtcgagtt cggaaattgt tgggttgatt
1020cgtggtaagc gcggtacaaa agtaacgttg aagcttcttg gtgctggtgc
atcaatgagt 1080caagcacgca atgtgacttt ggtacgtgat gttattcaag
aagaagatgc cggtgttcgt 1140tcacgtacag ttgaagtgac acgtgatggt
aaaaagcatc tattaggtgt gattgaaatt 1200ccatcgttct attttgacta
tcgttcacgt cgtgctggtc agcaatatcg ctcagtttct 1260gaagatactg
caaatgcgtt tgaggcatta aaagccaaga aagttgaagg tattattatt
1320gacttgcgta atgacccagg tggttcatta gaagaagttg cacgtatgct
cggacaagtg 1380attaagtcag gtccagttgt gcaaattcgt gatggcaatg
gcaacgtaag tgtatttgaa 1440gacaacgatg gtggtcagca aatctataca
ggtccactcg ctgtattggt gaacttggca 1500tcagcatctg caagtgaaat
ttactctgct gcaattcaag attatgagcg tggcattatc 1560attggtagta
caactacagg taaaggtaca gctcaggttc aactcgatac tttggcatat
1620ggtcaagcaa ccttaactca gcgtaaattc taccgtgtaa cgggtggtag
tacacaaaac 1680aaaggtgtag tgccagatat taagcttgtt gatatctata
acgaagagtt tggtgagcgt 1740aaatcgaaaa atgcgttgaa gtgggatacg
attccgactg caccatttaa gcgtgaaggt 1800tcagtgcagc catatgtagc
gaagctgtct caactttcgg aacaacgtgt tgctgttgat 1860ccacagttta
agtatttaaa taaacgtacg gcaattgcga aggttacgag tgaccagaaa
1920caagttgtgc ttgatattga taagcgccgt gcagagcttt tgagtttaga
aaagcaaact 1980ttagatgctg aaaatgaacg tcgtatagca acaggtcaaa
aacctttccc taactgggaa 2040agctatcagg cttctctaga tgctctagct
gaatctcgtg ccaaaatgaa agctaatcaa 2100cgtcctgcgt tgccagaaga
agaaacgttc gtaaatgaag ctgcgaatgt attgatggat 2160tatgcgaaat
tgcagaaccg ttaa 2184522187DNAAcinetobacter baumannii 52atgacaagaa
taattgtagc atccaaagag ggtttggacg ttctgcaaga tggtcagctc 60aataaggtgg
ttttaaacca acctactatt attcaaattg gtgtaagtca aaaagatatc
120gcatcgatgg aaaagcaggg tggaagtcta gtcatccatt taaaaaatgg
agaaacaatt 180gtcttagaaa atttctttaa tgaagcaacg aatacaacag
agcattcact cgtttttcca 240actgaacaag gaaaatttgt tgaagcacaa
tttgatgctc aaggtaaggt tatagattat 300agaggcttaa atcatgttac
ggatttggcc tataccagta ccagcccttc agctgcaaca 360atggccgttg
ataatgatcc aagcttttcg atgggtaatg tactaaaagc aggcttagca
420gttttagccg ctgaaggttt atatctttgg gcatttgata aagatgataa
agatgattca 480cccagtactc ccgatttaat agcacctgct gctcctacag
ctacgcttgc tgatgatact 540gtgacagtga ctggcaaaac tgaagcaaat
gcgaaaatct acattaaaga tgcagcaggt 600aatacagtgg cctcaggtgt
tgctgatgcg agcggaaatt acacgattaa attagataag 660ccgttagtga
atggggataa attaaatgtt attgcccaag atgcggctgg aaataattct
720aaagttactg tggtaacagg aacaaaagat acaattgccc cagatgttcc
acaagctcaa 780ttgagtgatg atggttcctt attgacaggt aaagcagaag
caaatgcaaa aatcactgtt 840tatgatgcca ctggcaaagt attaggaact
gtttttgcga ataaagatgg tatttattct 900ttaaaactta ctccaccatt
aaccagtgaa gcgggcggta aagtggttgc cgaagatgct 960gcgggtaaca
aatctgagga agttaaaatt attgcgggta aagataccat accgccagca
1020tctccttttg ttgaagtaaa taaagaaggg tcggtaatac atggtaaaac
tgaagcaaat 1080gcaaaagttc aaataaaaga tgccgatggt aaagtgattg
gaagtgggac cgccgatgct 1140caaggtgaat ttcaaattac actttcacct
gctttaaaag aggcgcaaaa gggcacagtg 1200gttgtggaag atgctgctgg
taatgtatct aaaccagttg aaattacgcc aggctttgac 1260tcgattgcac
cagataaacc gactgttcaa attaatacag atggtacttc tgtaaccggt
1320acggctgagg caaatgccaa aattgaaatt aaagatacaa caggcaaggt
aattggtagt 1380ggaacagcgg atgcgaatgg aaaatttaca atttctattt
caccagcttt aacggataat 1440aaacatgctt cggtatcagc tatagataat
gctggaaata agtctgaagt tgttgatatt 1500gtaggtacaa aagatacaac
accaccagca aaacctatat taaatagcgt agatgatgat 1560gtaggtgctg
ttaaaggagc tataacggct ggttctgaaa ctgacgatgc tagaccaaaa
1620cttacaggct caggtgaagc aaatgcaact cttactattt atgataatgg
tgttgcaatt 1680ggagttgtga cggtaacaag tggtagatct tggtcattta
catttgataa agacttagct 1740cttggtaagc atactattac tttgactcaa
actgatgcgg caggccttac cagtgaggca 1800agttctccat ttacctttta
tgtagttgct ccaaaggctg cgagtctgtc tgaaacttca 1860gtagatattt
taagtacaga gggaccatct ttggcagata gtgttggatt gcatacttta
1920aaggtagcgc aaaatacaac aactgagacg aataacccgc agaaatcggt
tcctttagat 1980gatttattaa aaagttctac ggctagtgaa tcagacccaa
tcgcaaaact tctctcatca 2040acagcgttaa aaacgactca ggcatctgag
ccaatcgaag taaatgcatc agttggtcag 2100acaacatcaa atcctaatca
tcctttacct gatacaactt cttcggtttt acaaaacctt 2160ttagatcaaa
cttatccagt tgtttag 2187532265DNAAcinetobacter baumannii
53atgtcgaagc gtattatcca gtcagtgctt tctgtttcag tactggcaag tatgatgtct
60atggcttttg ctgcacaaaa tgagcaagaa caagctgaac aaacattaga aaagcctgct
120gaacctgtga aattggaaac aattttcgta acagctgaag agcaagtgaa
gcaatcgctc 180ggtgtatcgg ttattaccaa agaagattta gaaaaactac
cagttcgtaa tgatatttct 240gactatgtac gtcgtatgcc aggtgtcaac
ctgacaggca atagtgctac tgggcagcgt 300ggtaataata gacaaattga
tattcgcgga atgggccctg aaaacacgct tattttagtg 360gacggtaaac
caattaactc tcgtaattca gtccgttatg gctggaaagg agagcgtgat
420acacgaggcg actcaaactg ggtaccagca gaagccatcg agtcgatcga
agttttacgc 480ggaccagcag ctgctcgata tggttctggt gcggcaggtg
gggtggttaa catcattact 540aaaaaagtga ctaatgaaac tcatggttca
gtagagtttt atacttcaca gcctgaagac 600tccaaagaag gttcatcaaa
tcgtgttggt tttaacgtaa gtgggccact aattaaggac 660gttttatctt
atcgtttata tggtaattat aataaaacag aagctgatga tgttgatatt
720aataaatcaa ttggtagtac cgcagctggc cgtgaaggtg ttaaaaataa
agatatttca 780ggccgtttag cttggcaagc aacagaccag caaactgtct
tgctcgatat ttcttctagc 840aaacaaggta atatttattc tggtgactct
cagttaaatg caaatgctga agcggatgcg 900atactttcgc agctcattgg
taaagaaacc aataccatgt atcgtgatag ctatgcatta 960acgcatgaag
gtgattggtc ttggggtaag agtaagttag ttgctcaata tgataagacc
1020cataacaaac gtctacctga aggcttggcg ggaagtgtag aaggaaaaat
taataatctt 1080gatgataaag ccacttcgcg tttagaaact cttcgcttta
acggcgaggc taatattcct 1140tttgaatact atttacccca agtattaact
gtaggtaccg aatgggttga agacagattt 1200aaagataatg tctcgacaac
tcaaggtaaa gacagcagtg gttcaggtta tggcgatcaa 1260ttagcgaaag
gtgatcgtag taaaatggag tcacgtattg cttctgcata tattgaagat
1320aacctgaaag ttacagacag cacagatgtt gtattaggtt tacgttttga
tgaccatagt 1380aaatctggtt ctaattggag tccaagctta aatattactc
aaaaactcaa tgataatttc 1440actttaaaag gtggggtagc aaaagcttat
aaagcaccaa atatgtatca aaatgccgaa 1500gggtatttat taagtacaaa
tggcaatggc tgtcctgcta atattgagtc gcgttgttta 1560ttacaaggta
atggtgattt aaaacctgaa acatcggtaa acaaagagct cggcattcag
1620ttccaaagag atatcgtgaa tgcgagctta acttggttcc gtaatgatta
taaagataag 1680attgttgcgg gtactcatgt tgtcggaaca gttgatggct
caagtacaaa tgcaaataca 1740ggagctgtga ccaatacgaa gtggaatatt
ttgcgttggg aaaatacgcc taaagcctta 1800attcaaggtt ttgaaggaag
tttggggtta gacttcggtg atatccgctg gactaataac 1860tttacctaca
tgatggactc gaaagacaag caaactggga atccattatc tttagttcca
1920atctatacaa ttaactcaat ttttgattat gacattactg atcaattgga
tgtaaatttt 1980gtatttactc aatatggtcg tcaaaaatca cgtcaatttg
cagagaatag acttgaatcc 2040ggtataggtt caggaggtgc gaattctgcg
cttaagccaa gtacggtaaa aagctatagt 2100actgctggta ttaatgttgg
ttataagttt tcagaccaaa ttagtacgcg tgttggtgtg 2160agtaatctgt
ttgataaaca aattttaaga gacagcaatt ctattagcca aacttataat
2220gagccaggtc gagcttatta tgcatcttta aaatattctt tctaa
2265542721DNAAcinetobacter baumannii 54atgccttcta aaattaagtt
taaacagtca actctttctc actctatgca tttaatctta 60aaaatgcaga gtatacctaa
acttatttgt agcagcttat tattaagttt atgtgttact 120ccttgttatg
ctcaaagttc ggctgagacc gttataccag aagcaaacca gacggtaaca
180gattcattgg tacaacaaac taatacaaat aacccaagtg atgttccaat
taccgatgtc 240gctactcttg taactcaagc acagcaacaa caagatagct
tggctatatt gcaacaacaa 300gaacaatttc cgaatcagat tgaagaattt
aagccaatta cgcttgataa tcttgaagac 360ttacctgtta tgcctgttga
tcagaatatg gcaaatgaaa tttatcgggt agcagaagag 420gcaaaaaacg
aggctcaaaa cttccagaat ggtacgcaaa aacaaccaga aatggtggtg
480agtgacgcat cacaagcaga attacatgaa attaatcagg cccctgtaaa
tattgaccag 540ctcatgcatg agattcaatc tgatagtaag attgtggttg
aagccaatga aacaggaaaa 600actttacctg agcttactgc tgccgttgaa
gaaccacccg aggaaaaagg tttctttaga 660cgtatattca ataaaatccg
tccacctcgg gtaattccaa tggagcagat accccgtatt 720actgctgagg
ttacgggtgc gccagatgat ttagctaaaa atatcaaagg taaattatct
780acatttaccc aagaatcatt tgaagatttt aatgcagcgc taccgcaact
taggagctta 840agtaatcagg ctgctcaagc tgtaggttat tacaatgccg
agtttcgttt tgaaaagtta 900agtgccagtc gcgtacgtgt taatgtaacg
ccaaatgaac cagtacggat taatgaacaa 960aacattgaat ttactggtgc
tggtgcaaaa cagccacaat ttcaggtcat tcgtttagtt 1020cctgaccaag
atgtaggtga tatttttaat catggccttt acgaaaccac aaaaagccga
1080attgtcgatg ctgcatcgga taatggttat tttgatgctt attggcgttt
acatgacgta 1140aaagtgagcc aacctgaaaa taaagcggat attaacctca
agtatgagac tggtgagcgt 1200tataagcttg gtaaggttga gtttcgcatg
agcgatccat caaaaccatt acctttaaat 1260atgaatattc ttgaaagcat
ggcaccgtgg aaagagggtg atgactatgc tttttggcgt 1320gtaaatgttt
tagcaaataa cctgactaac tcacgctatt ttaactatac cttggttgat
1380tcaattaaac ccgacccaat tgaaaaacca cttgagttac cacccgattt
acaagcgttg 1440gtcgatcagc agaatgttga tattgacgaa tcgaagctgc
ttcctttaga gcaacaacaa 1500cttgccaaag cacgccagtt ggcttcctca
agtaaagaag taacacaaaa tgtggtagat 1560gaaaaacaat ttgccggaac
tgaaagtgta caagccgcac ctgcatcttt aaaagctgca 1620actgtacaac
atgaagaaca agagtctgaa caagaccgtt tacaggctca agctcgggaa
1680gaaaaacgta taccagtgat tgtgacgtta aatgccgata aactaaatag
tctggaaaca 1740ggtattggtt atggtaccga cactggcgcc cgtttacgta
gccaatatag acgttcgatt 1800gtgaataaat acggtcattc atttgacgca
aacttggagc tttcccaaat tcgtcaatct 1860atagatgggc gctatagtat
tccttataaa catccgttaa atgattactt taatattgtg 1920ggtggttatg
agcgtgaaac gagggatgat attggtccgg atgtaagttt actcacggaa
1980tcggcagttt tagggggtga gcgagttatt aaaaaaccac tcggaaactg
gcaacatact 2040attggggtac gttatcgtct cgaccgccta actcaaaagg
ggaatgtgga tatctctgag 2100ctaccagatg catttaaaac tgctgcatca
gagcaagaag cattattatt tagttatgag 2160acctctaaaa cttcaagtaa
tacacgctta aacccgacca aagcttttaa acaaacttat 2220aaattagaat
taggtagcga aagtttactt tcagatgcca atatggcgat tgccacagcg
2280ggttggagat ttatttattc tttaggtgaa aatgatgacc atcagtttgt
tgggcggtcc 2340gattttagtt atatttttac cgatgagttt gataaagttc
catacaattt aagattcttt 2400actggtggtg accagacaat tcgtggtttt
gattataaaa gtctttcacc agaagataat 2460ggatataaga ttggtggaca
ggctctagca gtaggctctt tagaatataa ctatcaattc 2520aaagagggtt
ggcgagcagc tgttttttct gattttggta atgcttacga taagagtttt
2580agtaatccga cggcctatag tgtgggtgtt ggtattcgtt ggaagtcccc
aattggacca 2640attcgtttag acgtggcttc tggtatttct gatgataacc
atccgattcg tttgcatttc 2700tttattggtc cacaacttta a
2721552925DNAAcinetobacter baumannii 55atgtttatta aaagtatttt
atcttcgatt actagtatta tcccacttcc tgaaaatagt 60aacacaagca gtaatttagg
taacggctct ggtgacggcc tacttaatgg aatatcttcc 120ggaaatggtg
aacacaacta tggtattggc aatggtattg ccgatgacgc aagcattacc
180gccccaatta ccattcccct caacctctct ggtaactcaa ttactctcat
aggcaattca 240tcttcaagtt cggtgaatag ctctccaacc accacttcaa
ataacgttaa tgacaacgat 300gtaacaaata atggtaacgg ctctaccatt
ggtagcggta caggcaatgg ctctggtgac 360gggcttttaa atggcgccgc
ttctggtaat ggtgaacaca actatggaat cggtaatggt 420attgccgatg
acgcaagcat tactgcccca ctttcaattc caattaacct tgcgggtaac
480tctattaccc taattggtga ctcatcttct agttcggtca acaactctgc
aaccaataca 540tcaaataccg tgaatgataa cgacaccacc tataacggca
atggctcagg tggtggtaat 600ggttcgggcg atggcttgtt aaatggaatt
ggctctggca atggcgagca aaactacggt 660atcggaaatg ggattgcgga
tgacgcaagt attacagccc caattacgct tcctattaac 720ttgtctggta
actcaattac tctaattggc aattcatctg caagttctgt taattcctcg
780ccaactacaa cgtcaaatac tgtgaatgac aacgacacca cctataacgg
taatggtact 840ggtgatagcg gcgtgagcgc tctgggcggt tctggcaatg
gttcaggtga tggcgcaggt 900aatggtatcg cttctggcaa tggtgaacat
aactatggta ttggcaatgg taacggcgac 960gatgttgata ttactgctcc
gattaccggc gttctaaaca tttcagggaa ctcatttact 1020ctcattggta
attcttcatc aagttctgtc aataccgcac caacaaccac atcaaataca
1080gtgaacgaca atgacaccat tgataatggt aatagcggcg gcacaggtag
tggttcaggc 1140aatggctctg gtgatggttt acttaatggc gctgcttctg
gcaatggcga gcataactac 1200ggcattggca acggaaatgg tgatgatgta
gatattaccg caccaattac aggtgttttt 1260aatttctctg gtaactcttt
ctcaatcatt ggcaattcat cttctagttc aattaatact 1320gctccaacta
caacgaccaa tacagttaat gacaatgacg taactgataa tggaaatgat
1380ggaggcggac ttgttggtgg aagttctgga aatggctctg gtgacggact
gttaaacggc 1440gctgcttctg gcaatggcga acacaactac ggtattggta
acggaaacgg tgatgatgca 1500gatttcacct tccctcttac tggtgtactt
aacttttccg gcaactcgct ttcaggcttt 1560ggcagttcat ctagtgactc
ggtaaatgta gcaccaacca cagcaaccaa taccgtcaat 1620gataatgaca
ccattgataa tgccaataca ggcggccttg gtgacggttc gggcaatggc
1680tctggcgatg gtcttttaaa tggtgcagcg tctggtaatg gcgagcataa
ctatggcatt 1740ggtaacggaa acggtgacga tgcagacttt acgcttccat
ttactggcgg tttaaatatt 1800ctgggcaatg ctttatcagg tatcggcggt
tcttcgaccg actctattaa tatttcacca 1860acaactactt caaacacagt
caatgacaat gacactacca acaacggcaa cacttcaggt 1920ggtgtgattg
gttctggcga ctcaggcaac ggctctggtg atggcttatt aaatggcatc
1980tcatcaggta acggtgaaca taattatggc attggcaacg gtaatggcga
tgatgttgac 2040gttgttgccc ctatcactac accacttaat gtattaggca
actctttctc atttattggt 2100ggtgaaggta caggcgatat cttaggtccg
attactggca ttattggtgg tattggcggt 2160gatggagata tcctaagtcc
aattactggc attatcggtg gtattggtgg tgatggagat 2220atcctaagcc
cgattactgg cattatcggt agcattggcg gcatcggggg tgatctgggc
2280gataacccac ttacaggtat tattcaaagc ggtattgacg ttctacaaaa
tttagaaagc 2340ctaaaaacag gtttgattaa tacaggtatt gatacgattg
ccggaacaat tattggtgtt 2400ttccctgatg cagagcaccc tgtcggtgat
tttgcagatc ttggaaaact acttttcgag 2460acttcacgtg atagtgttaa
cggcacgctt gaagctattt ctgaccttgc aggcgctgac 2520cttgaggggg
caagtggctc gattactggt gtaattgata cccttattac caatggttca
2580acggcatcta ccattattca gcatattgta ggtgatgacc tagtcactga
aaacggtggc 2640ctcttgggtt caatcaccac gattattggt ggtgttgaca
gcggcgacgg tggtttactg 2700ggtggcctag atggcttaat tagcattaac
tatggcgact cagacaatag taattctata 2760gatgtagaag atattttagg
aaatatcctc ggctcggttg gttcaaatca aggtattgct 2820gttggtgaac
ctgatccaac gggcggtagt ttgattcata cgatttcact taacacagta
2880aatcagttaa ctgaccaact tttacatgct ttaccgactg tctaa
2925563216DNAAcinetobacter baumannii 56atgtataaac caaccacatt
tgtgtggcag ccatctgcag catcattatt caaaattaca 60gtccttagct ctgctttagc
tgcgttgggt attacaacag gctgttcttc gactccgcaa 120tctgcaaaaa
cctcgaaaac aaaacaggtg agtggagcag gctatcttga tgcaagcagt
180ctggactctt tagaagactt actttcagca acagatatgc gtgctgtaga
gggcgaccgt 240ttacttattt taaaacacgg tgatgtctgg aagcgtatgg
ctgtaggctt caaaatggac 300ctcaatcatt gggatccacg tattgaagcg
cagcgtagtt ggtttatctc acgtcagccc 360taccttgacc gcttaagtgc
tcgcgcaagt cgttatttat atcatactgt taaagaagca 420gaacgccgtg
gtcttccaac cgaacttgcg ttattaccag tgattgaaag ttcatatgac
480ccagctgcaa caagtagtgc ggcggcggcg ggtttatggc aatttattcc
tagtactggt 540cgtatttatg gtttacaaca aacgggtatg tacgacggac
gccgtgatgt tgtggaatct 600actcgtgctg cctatgagtt tttaggaagc
ttatataacc agttcggttc atgggaatta 660gctttggctg cttataacgc
tggtccgggt cgtattcaac aagcgattaa ccgaaatcag 720gctgctggtt
tgccaacaga ctattggtca ctaaaattac cgcaagaaac catgaactat
780gttccgcgtt tcttggctgt cgctcaaatt attaaaaacc cacgcgctta
tggggtttcg 840ttaccgccga ttgcaaatag gccccatttc cgtgaagtta
ccttatctgc accattatct 900ttaaatgaaa tcgcgtcggt gacgggtctt
agccgtgctg agttatatgc attaaaccca 960ggctatcgtg gtgaaacagt
agaccctgca agtccaatgc gtattttgat tccagctgat 1020ataagtcctt
cagtggataa caagttaaaa ggaatgaaag caggtggaag ttcaggctgg
1080tgggcaagtg ttacttcgcc gtctaaaccg accacaacaa cttcaacctc
agtcacagtt 1140agaactactc catcaactcc agctcagcca gtaagaccat
cgacgcctgc taaaacaagt 1200agcagctcgg taacggtaaa aactacaaca
cctcgtggtt ctgatgcgct agctgctttt 1260gcagcgtcag ctgatgtacc
aagtgcacca cgtattcctg ttgcggtcac tccggctgca 1320aatatcaaac
ctgtgagaac ggaaccgcca atttcagcaa ctgaacgcga gaaaatttta
1380gcggcagtgc gtgctgaagg ggaaaaggaa acagttgatc aagctttaga
acctcaagct 1440actcaagctg aaaaagatca agttgttgcc gagttaaaag
cacttgcacc tcagggtaca 1500gaaattgtcg atccgtatga cggcaaaatt
aagttaaccg caattcagac cagccaatct 1560gttgctgagc agcaaggtaa
agaagtaagt aaaggttttg cttatccaaa aactttagct 1620gaagatgcaa
ctcttgcaaa ctctgaagat gctcagcgca ataaagataa gccttatatt
1680aaaactgata cagatgttgt ggttgtacaa cctaaaggta agcgtagtac
ttatacagta 1740cagcctggcg atactttagc agttattgcc atgaagaatg
gtgtgaactg gcgtgatgta 1800gctaaatgga accagattga ccctgaaaag
actttatttg taggaaccag tctatatctc 1860tatgatgcta agcctcaaga
ggcggaaact acggcaaaat cggcagctaa acctgatgtc 1920tatgttgttc
aagcaaatga cagtttaaca ggagtggcaa atcaatttaa tttgtcagtg
1980aaacagctag ctgaatataa cgatttgtct gtaacagatg gcttgtttgt
agggcaaaaa 2040ttacagttaa aagaacctaa aggtaatcgt gctgctaaag
tagagccaaa ggcaattcaa 2100gcaagtacac gtcgtattgc aacaaagagt
tatacggtta aacgtggcga atacttgaaa 2160ttaattgcag accgttatgc
attatctaat caagagttgg cagacctaac accagggtta 2220tcagctggta
gtaatttaat tgtaggccaa aaaattaatg tacctgcaaa agaaatcact
2280gttgatgaag ttgatgacag caaggcttct ggtaaatatg aaaagcttgc
agcaggtcca 2340tcatataaaa ctgaaagtta taaagtgcag cgtggtgata
cattatcaag cattgcgacc 2400aagtctaaaa ttagcctagc tgagcttgct
gaactgaaca atttaaaagc gaacagtcat 2460gtccaactgg gacaaactct
aaaagttccg gctggtgcat cagttcctga ccaatatgtt 2520gtgcagtcag
gcgatagctt aaatgcaatt gcagctaaat ataacttaca aaccagttat
2580ttggctgatt tgaatggttt gtcacgtact gcaggccttc gtgctggtca
gcgtttaaaa 2640ttaactggtg aagttgaaac aactagcaaa gtttcggcta
aaaataccaa agaagaaacg 2700ccagagacct acacagttaa atctggtgat
agcttaggaa atatcgctaa ccgctatcat 2760ttacagttag attacctcgc
tgcattgaac ggtttgtctc gcaacagtaa tgttcgtgtt 2820ggtcaacgct
taaaattaac aggtgattta ccaacagtag aaacagctaa aacggatacg
2880gcgaaatcgt ctccaaaagc tgtagttgca ggaaaaaata ctgaaaagta
cacggttaaa 2940gctggtgagt cgttaaatgc tattgcgagt cgtgcgggta
tttcagttcg tgaacttgct 3000gaaatgaatg cattaaaagc aaatgccaat
ttacagcgtg gacaaaatat tgtgattcca 3060aaaactgtag tggaatacaa
agtcaaacgt ggtgatacct taattggtct tgcgagtaaa 3120tatggtttag
aaaccacttt attggcggaa ctcaacaacc taacaccgtc gactcaattg
3180cgtattggcg atatcattaa agtgcctaat ttatag
3216573333DNAAcinetobacter baumannii 57atgaaacgta tgttgattaa
tgcaactcat gccgaagaag ttcgcgttgc acttatcact 60ggtaatcgtc tttacgattt
tgatttagag aatcgtaccc gagaacagaa aaaatccaat 120atctataaag
gccatgtcac ccgcgtagaa ccatctttag aagctgtttt tgttgaatat
180ggcgcaggtc gtcaaggctt cttgtctatg cgtgaaattg ctaacagcta
ttttcaggca 240gacccacgtc aaacttcaaa cattcgtgaa cttattactg
aaggcacaga gcttttagtt 300caggttgaaa aagaagaacg tggtaataaa
ggtgcagcac tttctacgtt tatttccctt 360gcaggccgtt atttagttct
tatgccaaat aacccgaaag gtggtggtat tagccgtcaa 420atttcaggtt
cagtacgtga agaattaaaa gaaattttag cttctttaaa tgtacctcgt
480ggtatgagcg ttattgtacg taccgctggt attggacgta cccaagaaga
attacaactc 540gatttgcaac acttgcttga cctttgggca caaatccaag
gtacagccag ctcaggccct 600tctccgatgc ttgttcatca agaagcgggt
gtagtaacac gtgcaattcg tgattactta 660cgtgatgacg ttgctgaaat
cttaattgat agcgaacaag cttataacga agcatataac 720tttgttaaag
cagtgatgcc gcgtcaatta gacaaattaa aaacttatac tttaaacgag
780ccattgtttg ctcattttgg tattgaaagc caaattcaaa ctgcttacga
gcgtgaagta 840aaacttcctt ctggcggttc aattgtgatt gaccagactg
aagctttagt ttcaatcgat 900attaactctg cgaaatcgac tcgtggacat
gatgttgaag aaactgcact gaatactaac 960cttgaagcag cagaagaaat
tgctcgccaa cttcgtttac gtgacattgg cggtttagtt 1020gttatcgact
tcatcgatat gactaaagaa cgcaatcaac gtatggttga agcaaaactt
1080cgtgaagcaa cacaaagcga tcgtgcacgt atccagttcg gtcaattgtc
tcgttttggc 1140ttaatggaaa tgagccgtca acgcttacgc ccatcgcttg
aagaagcaac aggttatgta 1200tgccctcgct gtcatggtac aggcatggtt
cgtgatttac gttcgctttc tctttcaatt 1260atgcgtaaag ttgaagagat
tgcacttcgt gaacgtcatg gtgaagttca agttgaagtt 1320ccagttgaaa
ttgcagcctt tttgcttaat gaaaaacgcc atagtctggt gtatttagag
1380caaacttctg gtgtacgtgt gactgtattg ccacacccgc acttagaaac
tccacattac 1440gaaattgcat ataacccaga tggctttgct ccatctagct
atgaacgtac agaagcaacc 1500cgttctagcg agaaagagtt aggttatgag
tcttctgaat ggcatttaga agaagcagat 1560catggccatg ctcatgtaac
tgctacagct tcaactcatg ctgcggctca gaaaaaagca 1620aatcatgcaa
ctcaacctgt agcacaacct tctgctcaaa aagcagcaag cccatgtgca
1680tggttagaaa acctgtttgt tcaaaaacaa gcgcaaacag ttgatcaatc
tcgttcagca 1740caaaatgctg ctgctgcgat tgagcaaatg gtgaatacag
gcgcagtaag ccgcggacag 1800ttcggtcaag tagccgtacc tgctgttgcg
gaagttgcgc cagttcaatc aaataacgct 1860tatatttcac agtcacctgt
gaaacaagac gttcgtgaac atgttgaaaa agatgataaa 1920tctcagcaac
aacgtcagaa caacaaaaag cgtaaacata aagagcaacg tgaacaacat
1980caccaatcac atgaacagca acatcaagtt catgaagaag tggttcaatt
gtcacgccaa 2040gaacaacgtg agttaaaacg tcagcaaaaa cgtcaacagc
agcaagatca gcaacatcaa 2100aataatgatg tacaacacac tgaaaatgct
gtgccacgtc gtgaccgtaa taatcaacaa 2160cgtccaaacc gtccaaatcg
ccaccgcgat ccaagtgtat taaatgaaaa tcaaaataca 2220ctggttgttg
ttgatgaaaa acaaattaag gttgatgtga ttgatgcacc taagcatgat
2280gtcatgaaca ctgctttaat catcaatgtt gatcaaggtc aaagtgagat
tgttgcactt 2340acacctgagc gtcgtcacgt tgagcgagtt gaaacgactt
ctactgaagt tgctcaagag 2400ccaactccag ctcctgttgt agccgagaaa
gctgctgtag ttgaaaccaa agaagaagct 2460cagccaagcc aagaagctgc
tcagccacaa atcaaacgtg ctagcaatga ccctcgtatg 2520cgtcgtcgtc
agcaacgtga ggctaaacac gctaaggcag ctacaccatc tattgcgcca
2580tcgcaaattc caactttggc acaacacaca atcggtagtt taatccgtca
tgtgtatggt 2640gaagattgca ccgtattgat tgaacaattt ggtctagtcc
caacgtttaa tcgtgctttg 2700cagaaatttg cagaacagta cgcaagtacg
ttagtagttg aagttactgc tgaaacggaa 2760gagaaaaagc cggtaactcg
tgatgcagaa cttccaagcc ataaaccagc tgaagaagca 2820gaacctgcac
cagtacttcc gcttactccg ccgcaagcac cagctccacg tgttgcaaat
2880gacccgcgtg agcgccgtcg tttagcaaaa cttgctgcgg aacaagcatt
tgagcaagtg 2940aaacaacaac attctgctca agaagaagtt gctactcctg
ctcctgtagc agaagaaacc 3000gttgctgctc caactgctga aacacaagca
acagttgaac cagcacaaca accgcttgaa 3060cttaatcagt caactgaagt
cgtacaacct gaagctgctc ctgcagagga aaaagctaca 3120gaagaaacag
tagctgaagc tcctgcggca aaggaacctg cgccatcaaa agcagcaagc
3180aaagcaaaag cagcggctga agaaacagta gctccgactg aagcaacaac
tgatgccgaa 3240tcagaagacg ttaaggcaga taaggacaaa ccgagtcgcc
ctcgtcgccc tcgtggccgt 3300ccgccaaaaa aagctaatcc tgtagctgag taa
3333583687DNAAcinetobacter baumannii 58atgtctacgc ttgccaccct
aaaagcgctt cttgctaaac gcattctgat tattgatggt 60gcaatgggaa ccatgatcca
gcgccataaa ttggaagaag ctgactatcg tggtgagcgt 120tttgctgatt
gggcacatga tttaaaaggt aacaatgacc ttttggttct aacacagcct
180caaatcattc aaggtattca tgaagcctac ctcgatgctg gtgcagatat
tattgaaacc 240aacagcttta atggcacacg tgtttcaatg tctgactacc
acatggaaga tcttgttcca 300gagattaacc gtgaagcagc acgtttagcc
aaagcagctt gcgaaaaata ttcgactcca 360gacaaaccgc gttttgtggc
aggtgtactg gggccaacat ctcgtacatg ttcaatctct 420ccagatgtga
acaaccctgc ttttcgtaac attagctttg atgaactaaa agaaaattat
480attgaagcga ctcatgcact aattgaaggt ggtgcagaca ttatcctgat
tgaaaccgta 540tttgatactt taaattgtaa agcagcgatt tttgcagtca
aagaagtatt caaacaaatt 600ggtcgcgaat taccaattat gatttcaggg
accattaccg atgcatcagg ccgtacttta 660acaggtcaga cagcggaagc
tttctggaat tcggttcgtc atggcgattt gctttcaatc 720ggttttaact
gtgcccttgg tgcagatgcc atgcgccctc acgtaaaaac tatttccgat
780gtcgcagata cctttgtttc agcgcaccca aatgcaggct taccaaacgc
atttggtgaa 840tatgacgaaa ctccagagca aactgcagct ttcttaaaag
agtttgctga aagcggtttg 900attaacatta ctggtggttg ctgtggtacg
acaccagacc atattcgagc tattgccaat 960gcggtaaaag acattgcgcc
tcgccaagtg cctgaaaccg tacctgcttg ccgcttaagt 1020ggtttagaac
catttaatat ttatgatgat tcattgtttg taaacgttgg tgaacgtact
1080aacgttaccg gttctaaaaa attcttacgt ctcattcgtg aagagaactt
tgcagaagct 1140ttagaagttg cacagcaaca agtcgaagct ggcgcacaga
ttattgacat caacatggat 1200gaagggatgc tcgactcgca aaatgcgatg
gtgcattttt taaaccttgt agcatccgaa 1260cctgacattt cacgtgtacc
gatcatgatt gactcatcga aatgggaaat cattgaagcc 1320ggcttaaaat
gcgtacaagg taaaccggtt gttaactcaa tttccttaaa agaaggttat
1380gacgagtttg ttgaaaaggc ccgcctctgc cgtcaatatg gtgctgcaat
cattgtgatg 1440gcctttgacg aagtaggtca ggccgacact gctgaacgta
aacgtgaaat ctgtaagcgc 1500tcttatgaca ttttagtaaa cgaagtaggc
ttccctgctg aagatattat ttttgacccg 1560aacgtgtttg cagttgcgac
tggtattgaa gaacacaaca actacgcagt cgattttatt 1620gaagcaacgg
gctggattaa acagaactta ccgcacgcca tgatttctgg tggtgtgtct
1680aacgtttcgt tctcattccg tggtaatgag ccagttcgtg aagccattca
ctctgtattc 1740ttgtaccatg ccatcaagca aggcatgacc atgggtattg
tgaacgcagg tcaaatggct 1800atttatgatg atattcctac cgagctaaaa
gaagcggttg aagatgtcat tttaaatcag 1860aatcaaggtg agtctggtca
ggctgcgact gaaaaattac ttgaagttgc agaaaaatac 1920cgtggacaag
gtggtgcaac aaaagaagcc gaaaaccttg aatggcgtaa tgagtcagtt
1980gaaaaacgtc ttgaatatgc cttggttaaa ggtattacga cttatattga
ccaagacacc 2040gaagaagccc gcttaaaatc aaaacgtcct ttagatgtaa
ttgaagggcc actgatggac 2100ggcatgaatg tggtcggtga cttgttcggt
tcaggcaaaa tgttcttgcc acaagttgta 2160aaatctgccc gagtcatgaa
acaagcagtg gcatggctca acccgtacat cgaagctgaa 2220aagacagaag
gacagtctaa aggtaaagtc ctaatggcaa cggttaaagg tgacgtacac
2280gatattggta aaaatattgt aggcgtagta cttggctgta atggctatga
cattgttgac 2340cttggcgtaa tggtcccttg cgagaaaatc ttgcaaactg
caattgatga aaaatgtgac 2400atcattgggt tatctggtct gatcacccca
tctttagatg aaatggtatt tgttgctaaa 2460gaaatgcagc gtaaaggctt
taacattcct ttattgattg gtggtgcaac cacttctaaa 2520gcccacacag
cagtaaaaat tgaccctcag tatcaaaacg atgcagtaat ttatgttgct
2580gatgcttctc gtgctgttgg tgtagcgaca accttgcttt cgaaagaaat
gcgtggtgca 2640tttattgaag aacatcgtgc tgaatatgcc aaaattcgtg
agcgtttagc caacaaacaa 2700ccaaaagcgg ccaaactgac ttataaagag
tcggttgaaa atggttttaa aattgatgaa 2760agctatgtgc caccaaaacc
aaatcttttg ggaactcaag ttttaaagaa ttatccgctt 2820gcaacactcg
tggattattt tgactggacg ccattcttta tttcttggag tttaactggc
2880aaattcccga aaattttaga agatgaagtg gtcggcgaag cagcaactga
cttgtacaac 2940caagcacaag caatgttgaa agatattatc gacaacaacc
gttttgatgc tcgtgctgta 3000tttggtatgt tccctgctca gcgtacagat
gcagataccg tcagcgtatt tgatgaagct 3060ggtcaaaatg ttacgcatac
ttttgagcac ttacgccagc aatctgacaa agtgacaggc 3120aaaccaaact
tgtctttagc agattacatt cgtgctgacc gcgagcagca agactacttg
3180ggcggattca ctgtatcgat ttttggtgca gaagaactgg ccaatgaata
caaagccaaa 3240ggtgatgact actctgcaat tttagtacag tcattagctg
accgttttgc tgaagccttt 3300gcagaacatt tacatgaacg tattcgtaaa
gagttctggg gctataaagc ggatgagcag 3360ctcagcaatg aagagctgat
taaagagaaa tatgtcggta ttcgccctgc accaggttat 3420cctgcttgcc
ctgagcactc tgaaaaagca gtgttatttg actggttagg ctctaccgac
3480aaaattggta ctaaactgac tgagcacttt gcaatgatgc cgccatcttc
ggtaagcggt 3540ttctattatt ctcatcctca aagtgaatac tttaacgtgg
gtaaaatttc tcaagaccaa 3600cttgaagatt atgcaaaacg taaaggttgg
acactggatg aagcgaagcg ttggttagct 3660ccgaatttag atgactcgat tgtttag
3687593855DNAAcinetobacter baumannii 59atgaaactaa aattgaagaa
ttttaagcca aataatttat ggtatgccgt ctgttcaagc 60tcaatgatat tcacatggct
gatgacaagc tctgtggtgc aagcaagtga tttacaaatt 120tatgcctcac
ctacagcagg taaaaaaaca attgtgatga tgttggatac atcaggaagt
180atgaccaaca atagttatgg tgaaaaccgc ttagccatgc ttaaaaatgg
tatgaatgct 240tttttggcta gcaataaccc tgtcttaaat gatacgcgag
taggtttagg aaatttctcg 300gcaaatggtg acagccgaag tggacaaatt
ttagtggctg ctgctccttt aggtgatgca 360agtactttaa atacggtagg
ctcacaacgt tataaattaa aacaagctgt tgctaattta 420actgcgggag
gctcaacacc ttcagcccac gcttatgctg aagcagctgc ttacttaatg
480gggacaacca catattcaga gacgaattat gctattcgta aagatagtta
tatcaaacgt 540gtaagaagat ctgataatag aactgaatat tcatattgta
ctaattaccg tgattcgcaa 600attgatacag ccaacctatg gcaaccttgt
cgttcaaata gttattggag tagctggtca 660acaaataatc caggtgtgga
taatgctact gcttatgata cttcatctga ctggacttat 720tactatactt
attactacac cacttttaat tatgctgtag caaatgcaga tagcggtatt
780ccaaaatcta aatcaaacga tacagctagc aatccgaata ttgttgtaga
ccgaaatgct 840actaactcca atgcagtgta tcagtcacct ttacctgcag
tagcgaatcg ccagagttgt 900gatggacaag gtatttactt cttatcggat
ggcgaaccga acaatacaac aaatacacgt 960tcggcaagtg tcatgtcgac
tgctttaggt agtacttttg gagctgattt taattgttct 1020ggaggtttat
ctaacactac ggcagactct ggttgggctt gtatgggaga gtttgcaaaa
1080agattatttg ataaaacaaa gaaccctgcc ggagtttcta ttcaaacagc
atttgtcggt 1140tttggtagtg acttttctag tttgaattct tctgatgtaa
aaaatgcctg ccgtttaagt 1200tcgagaaccc agtctgaccg aaaaggagat
gatgcgtgtt caccgaatca atctacaaat 1260gcggtagctg caccaggtta
tggaaatggt ggttttttcc ctactcagag ttcacaaggc 1320gtaacagaca
gcgttatcgc atttattaat aatttagata aagttccttt agaaccctta
1380accacaggtg ctatctcagt tccatatgat gcattgaatc ccaaaaattt
acaggaatat 1440ggttatttac gagcttttga gccaaatcca gctaacacgt
acttaacatg gcgtggaaat 1500ttaaagaaat atcatgttgt tttatctgga
gcgaatgctg gtgcttttga ggccaattct 1560ggcggattag tctacaatgc
aagtggggct tttagaactg gaacaaagga ttattggaat 1620agctctactt
atactgacgg aggcaaagtc tttttaggtg gttcatatgc gaatgtgcct
1680ttacccattg ctggacaacc tgaaacacgt gatgcagaag ggaatatcac
aaaatattat 1740tacgcagtac aaagtaaaat ccgcaactta tttactgatg
tttccgccgt tgcagcagat 1800ggtagcttaa cgaaaatttc aacttctgga
actaatttgc taaaaattcc agctgctcca 1860ccagaagaaa ctaatccttt
tgatacggtg gctaatacag caagttatgt tttaggtaaa 1920tttgatccat
caactggaca aaatatttta aaagcttttc ctataagctt gaaattaaaa
1980atattaaatt atttaggtta ttcaacagat attaatgcaa caactctgcc
ttcatctttg 2040gttacatcga atgaacctta tttatcgatg gggggaagta
ttcactcttt accggttcaa 2100ctaacctaca atggaaccct agatgataat
gggaatttaa catctgcccg agaacaatcc 2160atcctctatg gaactatgga
aggcggatta catattgtgg atgcttcatc tggtattgag 2220caaatggtct
ttgttcctgc agatatttta aatgattcag ttgcttccaa agctttagtt
2280gttggtcaaa gtgatgcttc agctcccgct catggtatgg acggagcttg
ggtatctgat 2340ccagcctata atattactac agtgggaagt ggtagctcgg
cagtatcaaa agtaactgca 2400aagcaaatga atatttatgg cggcatgcgt
atgggaggaa gtagctacta cggactagat 2460gtattaagcc ctacttcacc
gaaactgctt tttagaatag gggcagacca gaatgactat 2520agccgtatgg
gtcaaagctg gtctaaaccc gtactcgcga acatccgtta taacggttct
2580attagacgcg tcctgattgt tggcggtggt tatgatcagt gttatgaaaa
accaaatatt 2640acgttgactg acgcttgctt taccaatgga aaagcaaaag
gaaatgctgt ctatattatt 2700gacgcaaaaa ctggtcagcg tttgtggtgg
acaagtgata caggttctaa tactgataac 2760gccaatatga agcatagtat
tgttagccgt attagtactt tagaccgtga tgctgatggc 2820ttagtcgacc
atctatattt tggagattta ggcggacaaa tttttcgcgt agaccttaat
2880aataatcaga caaaaaccaa ttcgacctat agcagttttg gtgtcagagt
tgtgcgttta 2940gcgaatttag caacaaatga ttcaacttat gatggcacaa
atgattatac aggtgggaat 3000gctcctcgtt tttatgagcc tccaacagta
acgatccacg attatggaat tcacactttt 3060attacagtag gaattgcatc
aggagaccgt agtacacctt tagatgttta cccactcaca 3120ggtcgtgaag
gtatgacgcc tgcaagtgca ttaagtggac gtcctgtaaa taatgtatat
3180ggaattattg atagagactt tgttaaaaag aacttaatgt ctttaactga
taatcagctt 3240gaaacaaaag atattacacg gacaggctta agaaaaaatc
cacaaattct aagaacaggt 3300gaaacaagag tagctcaaat tttcttccca
actacaggag taggtaaagg tggttggtat 3360cgctcgcttt ctagtacgag
cgatggtaca gaaaaagcta ataatagttt tcgtattaaa 3420ggaggactca
aagcttttga ggaaccaatg gcaattacgg gtaatttaat tattctagtt
3480tatgaccctc aaggaacggg aattgttgcg gcagatcctt gcctacctcg
tgttgtggga 3540gaaacagacc gacaaactta ttgtttacca tttggagctt
gtcttaattc tgatgggtca 3600atcgatcaaa ataaagagaa tcacagtggg
tttgaaacac aaactggtac taattgccca 3660gtaggggctt ctgaatgtaa
taaaaacgtt attggctctg gtattcgtag cgtaacattt 3720gtaccaacgg
aggataaccc acctacgact aatagttgtg ggaaattaaa gctgtctggt
3780aatgagcaag ggactggaca gtggcaatgt acgagtcatt tagttcctac
gcgttggtat 3840gagcgttatc gttaa 3855609144DNAAcinetobacter
baumannii 60atgacagacg ctgctggcaa tacttcggaa
caggctgtac aaaaagtagt tgtggatact 60accgcgccgc aagcaggtga actgacttta
tctgacttga gtgatacagg tatttcagca 120acagatcaga tcacgcaaga
taaaaacttc aatttaaagc ttgaaggaca ggaaagcggc 180agccgagtaa
catatttagt ttctaccgat gaaggaaaaa cttggcagga aaccacgata
240gcccaaaaag atttaactga tggtgtttac caatataaag ctgtagtgac
agacgctgcc 300ggcaatacct cggaaacggc tgtacaaaaa gtggttgtgg
atactaccac accacaagca 360ggtgaactga ctctatctga cttgaatgat
acaggcgttt cagtaacaga tcagatcacg 420caagataaaa acttcaattt
aaagcttgaa ggacaggaaa ctggtagccg agtaacatat 480ttagtttcca
ctgatgaagg aaaaacgtgg caggaaacca cgatagccca aaaagatttg
540gctgatggtg tttacaaata taaagctgta gtgacagacg ctgccggcaa
tacctcggaa 600acggctgtac aaaaagtggt tgtggatact accgcaccgc
aagcaggtaa actcacttta 660tctgatttga atgatacagg tgtttcagca
acagatcaga ttacgcaaga taatagtttt 720actttaaagc tagctcaacc
gattgtgatt ggggaacaag ccgctttact agaccactat 780gaagtttcaa
aagatgaagg aaaaacttgg caagagacaa cagctgatca aaaagattta
840gctgatggta tttaccaata taaagctata gtgacagacc ttgcaggcaa
tatctcagaa 900tctgctatac aaaaagttgt tgtagataat tccttaaatg
ttgaatcaac cacagtgatt 960gtaaagccga ttactgaaga caatacaata
agtctagttg aaaaagatca agttatttct 1020ataagacttg aaatagctaa
tttacccaca gatttaaata gctcactgac atcagtaaat 1080acgacattag
gcaatgttac ttataatttt cattttgatg aagtcacgca agaatgggtt
1140actgaaattc cagcagagtt tctttggtca gtagagccgc aaaccaatat
atcaattgag 1200attagtctta ctgatcaagc tggtaataca gccattatca
aacataccca aaattataat 1260gtggatcata ctccgaattc accaacccta
gattcactga ctttcaacaa tatagatgga 1320gctatcattt caggtagtgc
atataaagga agtaaggtcg atatctacaa taaaaatggt 1380gattggcttg
caagtacaat aactaatgaa gaaggtaaat ttactttaca agatctttca
1440attaactcaa atcaagaagt ttacgcagtc gctacttata atggttatag
cagtgaaaat 1500tcatcaattg ggttagttac tgaagttcca gctattagta
ttacacgaat tagtccagaa 1560ggcgtgatta gtggttatgc gactgaaggt
agtcatttta ttgtaaaaga tcagaatgga 1620aatattttac aagaatttaa
ttctaatgta tttgatagct ctggtattac accatttagt 1680gtaatggcat
taggcgaagt aagaccattt attttgtccc tcgatcagcc tttagaggaa
1740ggggctcaaa ttattatctc tatagataaa gataatattt caggccatcc
acaatatatt 1800actgcagact atactccagc agtattttta gaaactccac
aatttgatat tagtggtgaa 1860actttatcag tacatgttaa tgaacctaac
agctttattc gtgcattttc tggagaaggc 1920aatttaattg ctacaggttt
taccgatgag caaggctttg caagtttaca ggtgttccaa 1980tttttaaaag
aaggcgaaac ggtttctgta caagtagtag ataaaaatca aaatacgagt
2040gaaaccctaa tcgaggttcc aaactttgct tatattccac atgttgaacg
tattacacaa 2100gaaggcttaa tttctggagt tgctgaagat aatagtacgg
taattgtacg tgatgctgat 2160ggcaatgaat taggaaaggt tacattaggt
gatgataata gttggagtga ctttagtcat 2220tttagcttga gtgtaaaccg
ccctttaatt gatggagaga aaatttccgt tcaaattatt 2280gataataaag
ggttaatgag tcctgagcaa aatatcatcg tagatctgac tcctccacct
2340gctccaacgg agttaaattt taatgatgct ggtgatttag tttatggtca
tgcagaacct 2400ttctctgaaa ttttagttaa agatgggcaa ggaaatattc
ttaataaatg gttttggaat 2460aactggaccg atgagagtgg aagtttctca
atagaactag gtacattttt aaccaatgct 2520gagacggttt atgtcacggc
taccgatgta aatggaaacg taagtttagc agctcagata 2580caagcaccta
attatgcctt tgctccatat gttgatagct ttacttcgga tggcgtgata
2640agtgggcaag ctgaaaataa tagtactctc gttgttaaag acgccaaagg
tgacgttgta 2700gctgaaatta aagttggtga agataacggt tggaatggat
caagttattt taaactccag 2760cttgatcgtc ctcttgtcga tggtgagcag
tttttcttat caattaagga tgcacgtggg 2820caagtaagtg ctgatactgt
aattaccgct gatacggttg ctcctacacc agccagcaat 2880ttagttttct
cagaagatgg ttcatatctt acgggtgtag cagaactgaa tactacgatt
2940caggtttttg atcataatgg tcagctagtg aatatatgga ataacaccat
taactctgac 3000ggtacattta ctatttactt aggtagtaac aatttacatg
gagaagcatt cacagtcact 3060gttaaagacc aagccggaaa tgtgagtgag
gctatttcaa taaacgcgcc acttgacgat 3120attgcaccga atccaattaa
aaatatttta cttgatgcaa atggccaaaa ctttacagca 3180caagcagaag
caaatagtca gatcgaagtt tttgattcat tgggtaatca gacaggttgg
3240ggttctacag atagtgcagg taatgtttct ggttctttca atcaaactta
tttacacggt 3300gaggaactca cttttgttgt tatagatcga gcaggtaatc
gcagtatcga atttaagcaa 3360aatgctttaa ttgataccat tgcaccaaat
ccgattgcaa atatcatctt caacgaagat 3420ggccaaagtt ttacagctca
ggcagaagcc ggaagttcta ttgatgtatt agatcagact 3480ggaaataaga
ttggttttgg ttacaccgat agctcaggta atgtatctgg ttattttcaa
3540caagtttact tacacggtga ggaacttact tttgtcgtga tcgatcgagc
aggtaaccgc 3600agtgcagagg tcaagcagag tgctttgaat gatgacgtcg
taccaaatcc gattgaaaat 3660attgtattag atctcaatgg ccagaacttt
acagctcagg cagaagcaaa tagccaaatt 3720gaaatcaaaa ataataacgg
tgacgtcgta ggttatggat cagcagatag tgcaggtaat 3780gtttcaggat
atttgtatca agtgcattta catggcgaag agctcacttt tattgtagtt
3840gaccgagcgg gtaaccgcag tacagaggtt aagcagaatg ccttgattga
tgatattgcg 3900ccaaatccga ttgaaaatat tgtattagat atcaatgggc
aaaattttac agcgcaagca 3960gaagcaaata ctcaaattga agttaaaaat
gctgttggtg agattgtagg tttaggttat 4020gtggatggcg ctggtaacgt
gtcaggttat ttatatcaag tctatttaca tggagaagag 4080ctcacttttg
ttgtcgttga ccgagcgggt aaccgcagta cagaggttaa gcagaatgcc
4140ttgattgatg atattgcgcc aaatccgatt gaaaatattg tattagatat
caatgggcaa 4200aattttacag cgcaagcaga agcaaatact caaattgaag
ttaaaaatgc tgttggtgag 4260attgtaggtt taggttatgt ggatggcgct
ggtaacgtgt caggttattt atatcaagtc 4320tatttacatg gagaagagct
cacttttgtt gtcgttgacc gagcgggtaa ccgcagtaca 4380gaggtcaagc
agaacgcctt gattgatgat atcgcaccaa atccgattga gaatatttta
4440cttgatgcga acggacagaa ctttacagct caggcagaag caaacactca
aattgaagtc 4500aaaaatactg ctggtgaagt cataggatct ggttcaaccg
atagtatggg taatgtttct 4560ggttacttct atcaggtcta tttacatggt
gaagaactca cttttgttgt agttgatcga 4620gctggtaacc gcagtacaga
ggtcaagcag aatgccttga ttgatgacat tgctccgaat 4680gcgattgaaa
acattatctt taatgaaaat ggtcaaaact ttacagcgca agcagaagca
4740aatagcaaag ttgaagttaa aaatgctgcg ggtgaggttg taggttctgg
ttatgtggat 4800agtgttggta atgtgtcagg ttacttgaat caagtttatt
taaaaggtga ggagctcact 4860tttgttgtga ttgatcaagc tggtaatcgt
agcattgaag taaaacaaac agcctttctt 4920gataatacag caccggaaaa
tgcgactaat ttagtattta gtgaagatgg ctcatatcta 4980agtggtatgg
ctgagccaaa tgcgacgatt caaatatttg atcagtatgg tcaattatta
5040aatcagtgga ataataatgt taattgggac ggaacattta acatctattt
aaacagtaac 5100tacatgcatg gagaagtatt taaagtagtt gtagttgatc
acgctggtaa tttgagtggt 5160gaggttactg taaaagcacc gcttgatgat
attgctcctg tagctgcaag tgatctggtc 5220tttaatgaag atggttcatc
cctttctggt gtagctgagc caaatacctt catccagatt 5280tttgatcaaa
atggtcagca gatgaatacg tggagtcaga gtgtaaatgc tgatggtaca
5340tttactattt ttttcggtac ttacaattta catggtgaag agtttacagt
cattgttaaa 5400gaccttgctg gaaatgtgag tgaagctgtt tcagttaagg
cgccgcttga tgatattgcc 5460ccaaaaccga ttaaaaatat tgtatttgat
gcaaatggcc aaagctttac ggcacaagca 5520gaagcaaata gtcagattga
aatttttgac tcatttggta gtcagatagg ttggggctct 5580accgatagca
ctggtagtgt gacgggttac ttctatcaag tgtatttaca tggagaagaa
5640ttaacgttcg ttgttataga ccgagtaggt aaccgtagtg atgaaatgaa
gttaaatgct 5700ttgatggata ccattgcacc aaagccgatt gaaaacatca
tctttaatga aaatgggcaa 5760aattttacag cacaagcaga agccaatagt
tttattagtg tcaaaaatgc tgcgggtgag 5820tttgttggct atggttatgt
cgatagtact ggtaatgtgt ccggtcactt caatcaggtt 5880tacttaaaag
gtgaggaact cacttttatt gttatagata aagcaggtaa tcaaagtatt
5940gaatataagc aaaatgcttt aactgatgat attgcaccaa atccgattga
aaacatcgtc 6000ttaaataaaa atggacaaaa ctttacagcg caagcggaag
ccgatagcca aatcgaagtt 6060aaaaatactg cgggtgaggt cgtaggttct
ggttatgtag atagtattgg taatgtgtca 6120ggttctttta atcaagtcta
tttacatgga gaagagctta cttttgttgt agttgaccga 6180gcaggtaacc
gtagtacaga ggtcaagcag aatgctttga ttgatgatat cgcacctaat
6240caaattgaga atattgtttt tgatgtaaat ggtcagtact ttacggggca
tgctgaagca 6300gatactcgaa ttgaagtact agatcaattt ggcaatcgcg
ctggttgggg atatgttgat 6360agccaaggta acgtgatagg ttatttcaat
caggtttatt tacatggaga ggaattaact 6420ttcatcgttg tagatatagc
tggtaaccga agtgttgaag ttaagcaaaa tgctttaatt 6480gataatgtcg
caccgccagc agcagcaaat attacattaa cctcagacgg attgcttttt
6540ggtgaggcgg agccaaactc aactgttgaa attattgatc aatatggtgc
agttatcaca 6600acaacttatg tttggtacga tggcacattt aatcaatgga
ttaatctgag tcaataccag 6660acacaaaatt taagtattgt tgtcaaagat
caagcaggta accgcagtga agttgtacat 6720gaattagtac cagtatttac
caactcacca attgctgcaa cagagctaaa actggatata 6780gatggtcata
ttctgacagg taaggcgaca gtaggaatgt cggttgttgt tacatctact
6840gatggtcaga ccattaacgg agggtggaat aatgctgtga atgaagatgg
tagttttgct 6900attcagttaa atgattacta tctacaggga cagacattac
aagttcgagt ttatgatcag 6960aatacgaatc aatatagcct aatctctgaa
attattgcgc ctttagacaa tattgctcca 7020gtaattaatg aagtggtaat
taacaatgat ggttatggta ttactgggca aactgattca 7080aaagcaatca
ttcaggtaat ggatgcggat ggagatttac gagcagaatt tcaagcggat
7140gagactggat attttaacgc tagtatttat ccacctatat tacgtggaga
gcagttattc 7200atcactgcga tagatttagc caaaaatata agtaagccat
ttaatattac ttttaatgca 7260gatactaatg caccgccatc agcagagcat
attgtggtat ctgaaaatgg tttttttatt 7320gagggaaccg ctgtagcaat
tagtactgtg catatttttg atgtgcatag taaccatgtt 7380gccactaatg
ttgcagatga agctggaaac tttaatattc agttgtatcc acctctagcg
7440agtggacaaa ttttacgcat tgttgtggaa tacaatgggt atcaaagtgc
ttacaccgaa 7500attacggcac ctatagacac tgtcgcacca aatgcagcaa
ctcagcttct cttagaagat 7560ggaaatgtac tttcaggaca agcggaagca
tattcaattg ttaatatttt tgatgctaat 7620aataatttgg ttggtcagac
taatgttgga agtgatggtg ctttcttaac acacctatgg 7680tatgagtatt
ggcatggcga aacattaacg gtaaaagtag ttgatgccaa tcaaaatgtg
7740agtgtgggga caacgattgt tgctataaat gatacggtag ttccagatgt
agttacgcag 7800cttgctatag atgaatgggg ttcgctcaca gggagggtag
aaagttatgc tactgttgag 7860cttacctatc attttactga ccaaccgctt
tctgtaacga gcactacagc attggcaaat 7920ggaatgttct ttatctatct
ggatagaaat gcaacttcac ttgaccttac tgttattgat 7980cgtgctggaa
accgtagtga aaccattagc caaataatta gtgatttacc gactgttatt
8040attgatcact ttaaaggtga tgctacagat aatacttata acattgatac
tatagatgat 8100tttgttcaag aatatattgt tgagccgtat gcaatatata
aagacgtctg gattgataat 8160agctatatgt attcagattg ggtcattgaa
ggccattatg aacagatatg gtttgttgat 8220ggatattatg aatcgcaatg
ggccacaagt ggttattcaa ctgtacaaaa tatttatcaa 8280aatcaaaatg
gtataactta tattgataat ggcacggcag atagcgatta tagtcgatat
8340gaacaacaat attatgattt cgtgaatggc caatggcaag aaggctatga
attaacttat 8400atacgttcag aagaaggatg ggttgataca agtcattatg
aagatgttta tattgataca 8460agtcattatg aagaggtttg ggtagatact
agccactatc aagatatttg ggtagaaaat 8520agttattggg agagtcaact
tgttgaatct ggccgtagag atgtggattt aggcgggcat 8580gataaaatta
tcagttctgt taattatagt ttggttggtt tatatcaaac agtaaatgat
8640ccaacgactg tagattcgtt tttggaaagt ggtcgttatg tagaagactt
ggagctggtt 8700ggttctgctc atctaaatgc aacaggcaat gctttagata
atcttttaac aggtaactct 8760ggtaataacg ttttgaatgg gcgtgaaggt
aacgatacct atatcactaa tgaaggtact 8820gataccattg tgttccaatt
gctaaatagc caagatgcaa ctggcgggaa tggacatgac 8880acggtgttag
attttacttt aggtgatata agaactaacc ttcaagctga caaaatcgat
8940ttaagtgaac tattaattga ctattctaaa gatgtaagcg cattagctaa
atttattact 9000gtagagcaag atgctgggaa cacgactatt agtcttgacc
gagatggcga aggtacaatg 9060tttaatagtg tgtcactgtt aactctaaat
caagtaaata caacattaga cgaattacta 9120aacaaccagc aaattattgt ttaa
914461183RNAAcinetobacter baumannii 61augacacagc ucauuaauaa
agguggcuuu cgugaaagag ccaauagaag ccgaaaauau 60caacaaucug aaaacaagca
aguagcucug ccuucaaaaa aguaucaacc ucaaacuaaa 120cuccaagaua
aucaaagcga gaugauucaa gcaaaagcag guacugcuga aacuucagau 180uaa
18362201RNAAcinetobacter baumannii 62augaaauuag cuaaaacuuu
acucgcuacu acccuagcuu uaacugcugc uucaacuuuc 60gcugcuucua agcacgacca
agcacauaac acugcuggug aagaaaaagu uguuguuuca 120acucaagagc
aagcaaacac ugcaaaugcu gcuucugacg cuguagguuc ugcuucugaa
180gcugcuccug caacucguua a 20163201RNAAcinetobacter baumannii
63augauagaug aagaaaagcc uuuaaauuuu gaagaugaug acgagccucu ugauuuugaa
60gaugaagaau ucauagacga uaaaaaagag gacgaaaugu auaacucgau uacuaaggau
120ggcucuagug ucgauccugc ugaugauggg acacgacaua uucguccuga
agacggcgau 180ccgauugaaa uugaugagua a 20164222RNAAcinetobacter
baumannii 64augagcacua cuaauaauca agcaaaucaa cgcaauaauc agcagcaaca
acaacagcaa 60aaugacaacc guaaucaaca gcaacacggu aaccaacagc aaaacgauca
acagcaacaa 120aauaaccagc aacaacagca aaaugauaac cgcggucaac
aacaaggauc uaaucaaaaa 180gauucuggcc aacaaaacuc aaauaacaac
caacaacguu aa 22265327RNAAcinetobacter baumannii 65augucagcaa
aacuaguugu uacuuuguua gcaaccaguc uuuuaacugu aggcuguguu 60gcuuauacag
augauccuua uuaucgcggu gguuaugguu accaugauca ugacgacgau
120cguuaugacc guaacgaugg acgucgauau agugaguggg aacgcaaacg
uugggaagag 180cguaaaagau uauaugaaca acaacgcaaa gauauucgug
aacagcaaaa ggaucgucgu 240gaaugggaaa aacgacaccg ugaaugggag
aagaaacgcu uagaagaccg agaucaugau 300cauagagauu aucgucauga ugacuaa
32766345RNAAcinetobacter baumannii 66augaauaaau uacuuguugc
uuuaggucuu gcugcgacug uugcccuugu ugguuguaau 60aaagauaaag cuccagaaac
uggugcuacu acaggugaac acuuagaaaa ugcugcucaa 120caagcaacag
cagauaucaa aucugcuggu gaucaagcug cgagcgauau ugcaacugca
180acagacaacg cuucagcuaa aauugaugcu gcugcugacc augcugcuga
ugcgacugcu 240aaagcugcag cugaaacaga agcuacugca cguaaagcga
cugcugauac agcucaagcu 300guugaaaaug cagcugcuga ugugaaaaaa
gaugcucaac acuaa 34567381RNAAcinetobacter baumannii 67augaaaauga
cggcuaaaau ugcauuauuc agugcagcaa uuguaacuau ggguaguuug 60gcugcuuguc
aaucaacaac ucaaccaccu aagccagaac auggcaugau gcaagauggc
120ccacgugaug gucaccacca ucguaugaaa caccgugaau uuacgccuga
acaaaaagca 180gcaugggaac aacaccgugc agagcguaaa gcucguuuug
agcaaauuca aaaagcaugu 240gaagguaaag uuguuggaca aacugucaau
guucaaguug gagauaaaac acuugaaggu 300acauguaacc uccgcuuuga
gccaaaacgu ccucaaccac cagucaaugc cccugcucca 360guagcgacuc
aagcaaaaua a 38168420RNAAcinetobacter baumannii 68augaaagcca
uaaaaauuuu auguauuaca agcucuaucu ugguuucauc aucucucuuu 60gcugaaacac
cucaaccuca acaagugaau gaagcaacuu cuaagacaau gccuuauggu
120gauaauccaa gcuuaggccg cguacuguua uacaaaacag gaaaaggcau
ucaaaauuua 180ggagauucua uucaaggcgc uucugaaaaa acuucaaaua
aaauuaguga aaaauggaaa 240gauacgaaag aauuuaccgc cgaaaaagca
gaaguuguuc aacaaaaagc ggauacagcc 300aaaguauuua cugaacagaa
aauagaacaa gcuaagcaaa auaucaccag caguagaaac 360ggugaaaaua
uuccaaucga acaaggugag cuaaguaaau cuaguacgac ugccaauuaa
42069480RNAAcinetobacter baumannii 69augaaaaaau cauuauuagc
aauugcacuu augaguacuc uucuugucgc auguaauaaa 60caugaaaaua aaacagaaac
aaccucugau gcaucuacuc cuguacaaac ugcucaauca 120aauaauaaug
aagcgguaga uacagcacau acagccgaga auucuuuaga uugggauggu
180aaauauaaag guacgcuucc uugugcagac ugugaaggca ucaaaacuga
auuagaguua 240aaagaugaua aaacuuauga gcuaacagaa accuaucuug
guaaagguga ugcaaaccca 300uuugaaaccc augguaaguu uacuuucgau
aaagacaaua cuucuguuau uaccuuagau 360gauaaagcuc aaaaccguaa
auucuuuauu ggugaaaaua cagcgacagc uuuagauaug 420gaagguaaaa
aaguugaagg uucuuuagcu gaacauuaug uuuugaaaaa agaagauuaa
48070489RNAAcinetobacter baumannii 70auggcaaaua aaaaacuuuu
aaucugugcu gcaauugcgg cuggacuauu guuaaccgca 60ugcguuaaaa aagagacacc
gaaagaagaa gagcaagaca agguugaaac ugcuguuuca 120gaaccucaac
cacagaagcc ugcaaaauuu gaaucuuuag agaguguaga uacucaagaa
180gcucaaguuc aagagcaacc acaaguugaa guucaucgug aagaaacugc
uaacacgaca 240acugaaauuc gccgugaaac ucguccugcg cguucugaug
aaucuucaca gacacaaguu 300gcugaacaac cuaaaucuga gacaccaaaa
guagaaccua aaccagaaaa aaaaccugag 360ccuaaagcug aaccuaaacc
ggaaaaagcu cagucaaaac cagcugcuaa ggcaacugag 420ccugcgaaca
cagaagauga ugccguugcu gcugcuauug cugcugcaac accagcacuu 480aagaacuaa
48971501RNAAcinetobacter baumannii 71augacuacug aaaauaaauu
agaugaauua aaggcaaacg cggcugaugc aaaaguacaa 60ggugaaaaag cuuuggacga
uuuaaaagaa aauguaaaag agaaacaaac ugcggguaaa 120gaagcaauug
cagauaaagu agaugagcua aagaccaaag cggccgaugc aaaaguacaa
180ggugaaaaag ccuuggaaga uuuaaaggaa aauguaaaag aaaaacaagc
ugcugcaaaa 240gaggcaguug aagauaaagc uagugauuug aaaggcaaac
uugaugaugc ucagcauagc 300cugcaagaca aguuugauca uuuacguacu
gaagcagcgc auaaacuuga ugaugcuaaa 360gccaaagcug cagaauuaaa
ggaagaggcg gcuacaaaau uugaugaguu aaaaacucaa 420gcaacugcga
aauuugauga guugaagaaa acagcuaccg aaaaacuuaa uaaauugaaa
480aaucaugauu cugcugaaua a 50172693RNAAcinetobacter baumannii
72augcacacgc gucguauuuu auuagcguuu ucacuugccg cuucggcagc aucgguugcu
60uuugcagauu aucaaaauau uaaccaaucu acugauucag aucgauugga acaguuauca
120aaaacacuau cucaaggcuc auauacucau ccugaugauu uagaucuucc
ggcgagugca 180aaaguuucag ugacuuuacg ugagaaaaca guugaacuca
acaaugauuc acuggcaaag 240aaauacggca caacgacagc uaaaaacuca
uuuaaaaccu cuucuucaaa uccuuauucu 300ugguuaguuu cucauccucu
uccugauaca guacguguuu cuucuaacuu ugguggucgu 360accaugggug
gucgugcaga gcaucauggu gguuuagaua uggcugcacc aagugguacg
420ccaaucuaug ccacuggucc ggguauugug acuaaaucag gcuggggcac
agguuauggc 480caauauguug aaauuaacca ugguaauggu uauuuaacac
guuaugcgca ugcuucacgc 540uuaaugguuc ggguagguga ucagguuucu
gcgggugacc auauugcuaa uguugguugu 600acaggccgcu guacuggucc
acauuuacau uacgaaguag uuaaagaugg ucaacguaag 660aauccaucaa
cuuacuuagc aauguugccu uaa 69373717RNAAcinetobacter baumannii
73augggcauga cuuuuacaga cauagaaaau aaaucugcca aacgccuaau ugguauugcu
60gcagucauuu uucugcaucu ucuuguugcc uauauucuga ugucagguuu agcaaacaau
120auucaaaaac cagcagaaaa accuguggaa uuacaaauua uucaggauau
uaagccaccu 180ccuccaccaa agccggaaga gccgaaacca aaggaaaaac
caccugagcc accaaaaaug 240guagaaaaag uugccaaggu uccugagcca
ccaaaagaag uagagaaagu agcaacacca 300guacaaaaaa cgacgccagu
agcucaaacg acuaaagucg cuacuccggc uccugcugca 360ccuaguacuc
cuucuccgag cccuguugcu gcaccagcuc caguggcagc ugcugcacca
420gcacuuaaac ccgcuggugu aacucguggu guuucagaag gcucugcggg
cugcgaaaaa 480ccagaauauc cacgcgaagc acucaugaac gaagagcaag
guacggugcg uauacguguu 540uuaguugaua cuuccggcaa agucauugau
gccaaaguaa aaaaaucgag ugguagcaaa 600accuuagaua aagcagcaac
uaaagccuac agcuuaugua cguucaaacc agcaaugaaa 660gauggcguac
cucagcaaga cugguaugaa auugaauauc cauucguaau ugaauaa
71774762RNAAcinetobacter baumannii 74augaaaauga ugaaaacagc
uaucguuacu gcaaguguac uugcuucugc cucuauuuuu 60gcacaaagug cgggcguuaa
ugcaggugca ucugcucaag ucaacguaca accagguggu 120cuuguuagug
gcguagccaa uacagucaaa aauacugcac auacuguagg gaacacagca
180aaacaugcug gucacguagc ugcugacaca accguuaaag cuacaaaaaa
aacaacaggu 240aaaguaacug aacuuucuuc uaaagcugcu acugguacua
aacauguagc aagugaagcu 300guaacuggua cuaaacauuu ugcuaccgaa
gcagcaacag guacaaaaaa uuuagcgacu 360aaggcugcaa cuggcacuaa
aaaccuagca guugaagcua aagcagauac aaaagcacau 420cuugaugcug
uaaaaacuaa gguagcagaa aaacaagcug accaaaaaga auuuacugcu
480gaaaaacagg ccgaugcuca agcacgugua gaugcuguua aagcucgugu
agcacaaaau 540caagcugagc aaaaagaauu cguugcugac acuaaagcug
augcucaagc aaaauuaaau 600acagcucaac cagcucaugg aguuaacgcu
caaacaggug uaaacguugg uguuaauguu 660gcugguauua augcaaaugc
aaacguaaau gcaggcgcuc aagcgucuac acaaaaaggc 720gaaaagaaau
cuuuuauuaa aggucuuuuc gguacuaacu aa 76275885RNAAcinetobacter
baumannii 75augcaaauga agaagcauuc uuuauuauuu auugccuuaa ugagcaccac
uucucuauac 60gcaaauaucc cuaucgaguc ucgugguuua agucaaaaug augguagugc
aucuaauacu 120ucuucaagca auauuucagu uccuacaaau uuaaacuggg
aacucaugca aaaaaaccaa 180caauuagaaa augauauucg uacauuaaga
ggucagcuug aagaacaagc uaaugauauu 240gagcaauuaa agaaagaucu
agcaaaccga uauaccgacu uagaucaacg uuuagaauua 300uuacaccaaa
aaguugaccc ugacagugcu acacaagaug auaguucgaa ugcaacgucc
360gauaacacua cuccugcuag ugcaccagcc ccucaaacca cggagaguaa
uaaaguagcu 420gccguaccag ccacacaaac uucugagcag cagccuagcg
caccaacaac cacuacucaa 480ccagcaccag cugcugcgca aaaccaguca
aauucccucg aauuagaaaa agcugcuuau 540acuguagcuu uagaugcgua
uaaacaaggc ggugcuaaaa aagcaauugc uccaaugcaa 600aacuuuauaa
aaaaccaucc uaauaguauc uauacaggua augcuuauuu uugguuagcc
660gaguuucauu uagcgacaga uccaguaaau uauaaugaag caaagaaaaa
cuauaauguc 720guagcuaacc aauacccaaa uucaaguaag gcaccucgag
cauuguacca acuuuauagu 780aucgcuaaag auguugauaa gaauacugug
ucagcaaauc aauacaagaa caaguuacuu 840agccaauauc caaaaucuga
agaagcaaaa uucuuuaaca aauaa 885761071RNAAcinetobacter baumannii
76augucaauga auaacaaaca acgcuggaug gguggcguug uuuuauuagg uggugguguu
60uuauuggcag cauuacuucu aaaaggaaau gaagaaauaa aacagguaga uguucaaccc
120caaacuucaa caucaccgaa auuacaagcu aagccaaagc aaucagcaca
agaagggcag 180augguacagc uacagccacu ugcaguugau guugaaacag
aaaaacgucu ucuugaagaa 240cagcgccguu cucgugaaaa agcuguagca
gaacaagagg cucgugcugc cgaauucuug 300gcaaugcaac aacaggcaga
agcggaugca gcucguaaag cugcugcuga auaugccgcg 360auuaaugcuc
gccgagcugc ugcacaagaa aguuccgaua auauuccucc ugaagucgcg
420gguagugaga auaaggcaaa aggacagcaa acugauacaa aaaagucagu
agaucuggcu 480aaagcggaug cagauaaaaa agcugcugaa gcgaaacgcu
uagcugaggc ggauaagaaa 540gcggcugagg caaaacguca ggcagaagca
gacaagaaag cagcagaggc uaaacgccaa 600gcagaagcag auaagaaagc
agcugaggca aaacgucagg cagaagcgga uaagaaagca 660gcagaggcga
agcgccaagc agaagcggac aaaaaggcug cugaagcuaa acgucaagca
720gaagcagaua agaaagcagc ugaagcgaaa cguaaggcag aggccgagaa
aaaagcugaa 780gcagagaaag cacgugaguu gcuugaaaau ggugauaaaa
aauggauggu acagguugca 840uuggcugcua accaagcaaa ugcagaugcu
guagucucua aauuacgugc aaaaggcuau 900aaggucacga cgaguccaac
caguaaaggu auccguauua ugguuggucc ugcaaaagau 960agagauacgg
cagauacuac acguaagaaa auuacuucug acgccaguuu aaauaugaag
1020ucagcuuggg ugauugacug ggugccuuua gaucagcgua agucagauua a
1071771104RNAAcinetobacter baumannii 77auggcuaaua cuagauauga
agaugauaac aauaguucag guacuucaaa ucguggauuu 60gcaaguaugg auccugaaag
agucagagaa auagccagua aaggugggcg agcugcacau 120gccaguggca
augcgcauga auuuacuuca gaagaagcuc gugaagcugg ccgugcugca
180caugccagug guaacgcaca ugaauuuacc ucagaagagg cucgugaagc
uggugcuuua 240agucauaaaa acgaugaucg uaauggucgu ggucgcagcc
guuaugauga cgacgaagau 300gaugaccgcg gccguucaag uggucgaggc
cguggccgca gucguuauga ugaugacgac 360gaagaugaug aucgcggucg
cucaggcggu cguggccgug gucgcggucg ugaugaugac 420gacgaagaug
augaucgcgg ucgcucaggu ggccgaggcc guggucgcag ucgugaugau
480gacgaugaag augaugaucg cggucguuca gguggccgag gucguggucg
cagccgccgu 540gaugaugacg augaagauga ugaucgcggu cguucaggcg
gucgaggucg uggccgcagc 600cgucgugaug acgacgauga agaugaugau
cgcggucgcu cagguggccg aggucguggu 660cgcagccguu augaugacga
cgaugaagau gaugaccgug gccguucagg cggucgaggu 720cguggccgca
gccgucguga cgaugaugac gaagaugaug aucguggucg uucagguggc
780cgaggccgug gccgcagucg uuaugaugac gacgaugaag augaugaucg
uggccguuca 840gguggccgag gucguggccg cagccgucgu gaugaugacg
augaagauga ugaucgcggu 900cguucaggug gucgaggccg uggccgcagu
cguuaugaug augacgauga agaugaugau 960cguggucguu cagguggccg
aggccguggu cgcagccguc gugaugacga ugacgacgau 1020gaugaccgcc
guggccguuc agacggucgu ggucagaacu cucguaauca aaaacgcgau
1080gcuuauggac gcuuuacguc uuaa 1104781263RNAAcinetobacter baumannii
78auguuauaug ugauuccguu uaucauauua cucguggucg ccguuauuuu aaaaaaacgc
60gagaauaguc aaaaacaaga ggccacuucc ccaaaaaaua uaaauagaaa auccggcaaa
120aaagcgagug cuaaaucaag caaaagcucg cgugaaaaaa uaaaagccaa
ggucauugag 180gaaaauauuc cugcuauccc ucaaaguaau ccuguaccgg
aagcuuuacg acacaauauu 240caacagcuca uucaagaaaa acaguuuuca
gcagcugaag cucaagucaa ucaggcgcua 300aaaaaagaua auacucaaca
ugaacuguau uuauuacuuc uugaaauuca uauugcucag 360aaagaugaau
uugcaauuca acaguugauu agccauauuc guagcuuggg uuuaaaugaa
420auagcagcuc aagcagaaac ucgacaaaaa gaauaugaau cauccagcca
accugaugcu 480auugauuucc cucaagcuca aacauaugaa gaaccgaaaa
acacagauac aacggcucag 540uucgaugaau uaacaacaag uucuuccgag
gcuucuuuug augaccuaca gaaagacuau 600accccuguaa aacaagaacc
ugcuauugaa auugaaccuu uagaguuuaa cuuuucauuc 660gaacagaauu
cggcuacgga aaauaccaac caaccagcac aacaaccuga guuaucaucc
720acucaagaaa caaaugagcu ggccgauuua gaguuuucuu uugacuuggc
cccucugcau 780gaaacugagg aaaaaucuca agcaguagag guaaaagcag
accaagaaaa uagcaucaau 840gcauuagauu uuaacuuuga cuuaaauccu
ucaaguucag agacgaaauc uguucaacaa 900gcucccucau uagaugaaau
uaagcucaua gaacaagccc cauuagaagc gacuucuauc 960gcaccucuug
aguuuucguu agaugagccu gccuuaguuc cagcaccaga gcuugaaacu
1020caaaaccaua uagauguagu aaaugaagca gccacucaaa cccaaauaga
ggauccgcuu 1080uuagaagcuu uuccagaauu aaaacaaaua aaugaaaaug
aacucgauuu aaaauuggcu 1140gaacaauaca uuaaguuugg cgcaaaccaa
gcagcgcgua auuuacuaca gggugaugag 1200caaaaauuca acacagaaca
acaacaacau gcgaaaaacc uacuuaaucg cauagcuucu 1260uag
1263791338RNAAcinetobacter baumannii 79augccaaaaa uaaagccaau
uaaacucgua auuauugucg ucuguaucgc cauuauugcu 60gucuuagcuu ggaaauucuu
aaagccuaaa caacagcaac cucaauauau uacagcagag 120guaacucgug
gggauauuga gaauaaugua cuugcaaccg guacacuuga ugcaaccaag
180cucauuagug ugggugcuca gguaucuggu cagguuaaaa agauguaugu
gcagcuuggu 240gaucaaguaa aacaagguca acuuauugca caaauugacu
cgaccaccca agaaaacagu 300uuaaaaacau cugaugcuaa uauuaaaaau
uuagaggcac agcgucuuca gcaaaucgcu 360ucuuuaaacg agaaacaacu
cgaauaucgu cgucaacaac aaauguaugc ucaagaugca 420acaccucgug
cagauuuaga gucggcugaa gcugcuuaua aaacagcuca ggcacaaguu
480aaagcauuag augcacaaau ugagucugca aaaauaacgc guucaacagc
acaaaccaau 540auuggcuaua cccguauugu ugcgccaacu gaugguacgg
uuguugcgau ugugacugaa 600gaaggucaaa cgguaaacgc aaaccaaagu
gcuccuacua ucgucaaaau ugcaaaacuu 660caaaauauga cgauuaaagc
acaggugagu gaagccgaua uuaugaaagu ggaaaaaggu 720cagcaggucu
auuucacgac cuuaggugau gaaaccaagc gcuaugcaac cuuacgucaa
780aucgaaccug cuccagauuc aaucucuagu gaaucaaaca gcaccacaag
uucaacaaca 840agcucagcug uuuacuacaa cgcuuuauuu gauguuccaa
auacggacgg caaauugcgu 900auugauauga cugcacaagu uuauaucgua
uuaaauucag caaaaaaugc cuuauugguu 960ccaucuucug cguuaaguag
caaacaauuu ucuggccaaa gaaaacaggg gcaaucggca 1020gauaaagcaa
guucuacucc aagugcagaa cgcaagcauc aagguaacgg cguccguuua
1080gaacgcuuaa auuuaacucc ugaacaaaaa caacuuauug aacaaggcaa
agcaacucug 1140aguguaguuc gcguuuuaca agcagauggu acgacuaaac
caacacaaau uuugguaggu 1200auuaauaacc guguaaaugc acaaguacuu
gccggauuaa aacaagguga ccaaguugug 1260auugcugaua guucagaaaa
cucugcagcu ucugcaaaca gugguaauaa ccgccgccgu 1320ggcccaaugg gaauguaa
1338802136RNAAcinetobacter baumannii 80augaauaucc caccucgacc
auuuaaguug ucuguaaucg ccugcgcgau uuguuaugcc 60aaccucaccu augcccaaga
ugcacaggua caagcuuugc aaacgauuca ggucaaagca 120ucaaaugcag
agcagucuuc ugaacagacc aaggcauaua auguuaaaaa cucaaguagu
180gcaaccaagc uuaauauuga ggcuaaggaa acaccccaaa ccauuaaugu
cguuacucgu 240cagcaaauug aagauuuugg ccuuaccagu acucgugaug
uuuuaagaaa uaccccuggu 300guaacagucu cuaaucaaga aacugagcga
accacuuaua uggcucgugg uuuugagauu 360ucaaauaucu ugacggaugg
cguaggcuuu ccucuuucag guuauaacua uaauaauacg 420aauccugaua
cuuacuuuua ugaucgugua gaaguaguua aaggagcuga cucguuaacu
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2136812184RNAAcinetobacter baumannii 81augaaacuuc aaacuauagc
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2187832265RNAAcinetobacter baumannii 83augucgaagc guauuaucca
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2721852925RNAAcinetobacter baumannii 85auguuuauua aaaguauuuu
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9060uuuaauagug ugucacuguu aacucuaaau caaguaaaua caacauuaga
cgaauuacua 9120aacaaccagc aaauuauugu uuaa 9144
* * * * *