0 16 Characterization characterization NN 17 19 of of IN 20 28 defensin defensin NN 29 39 resistance resistance NN 40 50 phenotypes phenotype NNS 51 61 associated associate VBN 62 66 with with IN 67 76 mutations mutation NNS 77 79 in in IN 80 83 the the DT 84 88 phoP phop NN 89 98 virulence virulence NN 99 106 regulon regulon NN 107 109 of of IN 110 120 Salmonella Salmonella NNP 121 132 typhimurium typhimurium NNP 132 133 . . . 135 138 The the DT 139 147 defensin defensin NN 148 161 sensitivities sensitivity NNS 162 164 of of IN 165 175 Salmonella Salmonella NNP 176 187 typhimurium typhimurium NNP 188 195 strains strain NNS 196 200 with with IN 201 210 mutations mutation NNS 211 213 in in IN 214 217 the the DT 218 227 phoP/phoQ phop/phoq NN 228 241 two-component two-component JJ 242 251 virulence virulence NN 252 259 regulon regulon NN 260 264 were be VBD 265 271 tested test VBN 272 274 by by IN 275 280 using use VBG 281 289 purified purify VBN 290 299 defensins defensin NNS 300 304 NP-1 np-1 NN 305 308 and and CC 309 313 NP-2 np-2 NN 313 314 . . . 315 322 Strains strain NNS 323 327 with with IN 328 337 mutations mutation NNS 338 340 in in IN 341 347 either either CC 348 352 gene gene NN 353 355 of of IN 356 359 the the DT 360 370 regulatory regulatory JJ 371 375 pair pair NN 376 377 ( ( ( 377 381 phoP phop NN 382 383 [ [ ( 383 398 transcriptional transcriptional JJ 399 408 activator activator NN 408 409 ] ] ) 410 412 or or CC 413 417 phoQ phoq NN 418 419 [ [ ( 419 427 membrane membrane NN 428 434 sensor sensor NN 435 441 kinase kinase NNP 441 442 ] ] ) 442 443 ) ) ) 444 447 had have VBD 448 457 increased increase VBN 458 471 sensitivities sensitivity NNS 472 474 to to TO 475 483 defensin defensin NN 483 484 . . . 485 488 The the DT 489 498 predicted predict VBN 499 510 periplasmic periplasmic JJ 511 517 domain domain NN 518 520 of of IN 521 524 the the DT 525 529 PhoQ PhoQ NNP 530 537 protein protein NN 538 547 contained contain VBD 548 549 a a DT 550 558 markedly markedly RB 559 566 anionic anionic JJ 567 573 domain domain NN 574 578 that that WDT 579 584 could could MD 585 593 interact interact VB 594 598 with with IN 599 607 cationic cationic JJ 608 616 proteins protein NNS 617 620 and and CC 621 625 that that DT 626 631 could could MD 632 634 be be VB 635 646 responsible responsible JJ 647 650 for for IN 651 661 resistance resistance NN 662 664 to to TO 665 673 defensin defensin NN 673 674 . . . 675 682 Because because IN 683 692 insertion insertion NN 693 702 mutations mutation NNS 703 705 in in IN 706 710 phoP phop NN 711 714 are be VBP 715 720 polar polar JJ 721 723 on on IN 724 728 phoQ phoQ NNP 728 729 , , , 730 732 we we PRP 733 744 constructed construct VBD 745 752 strains strain NNS 753 757 that that WDT 758 767 expressed express VBD 768 771 the the DT 772 776 PhoQ PhoQ NNP 777 784 protein protein NN 785 787 in in IN 788 791 the the DT 792 799 absence absence NN 800 802 of of IN 803 807 PhoP PhoP NNP 808 810 to to TO 811 815 test test VB 816 823 whether whether IN 824 834 resistance resistance NN 835 837 to to TO 838 846 defensin defensin NN 847 855 requires require VBZ 856 860 only only RB 861 864 the the DT 865 869 phoQ phoq NN 870 874 gene gene NN 875 882 product product NN 882 883 . . . 884 886 We we PRP 887 892 found find VBD 893 897 that that IN 898 908 resistance resistance NN 909 911 to to TO 912 920 defensin defensin NN 921 929 requires require VBZ 930 933 the the DT 934 942 function function NN 943 945 of of IN 946 950 both both DT 951 961 components component NNS 962 964 of of IN 965 969 this this DT 970 980 regulatory regulatory JJ 981 987 system system NN 987 988 , , , 989 996 because because IN 997 1004 strains strain NNS 1005 1015 expressing express VBG 1016 1020 PhoQ PhoQ NNP 1021 1028 without without IN 1029 1033 PhoP PhoP NNP 1034 1038 were be VBD 1039 1044 still still RB 1045 1053 markedly markedly RB 1054 1063 sensitive sensitive JJ 1064 1066 to to TO 1067 1076 defensins defensin NNS 1076 1077 . . . 1078 1082 This this DT 1083 1090 implied imply VBD 1091 1095 that that IN 1096 1097 a a DT 1098 1101 pag pag NN 1102 1103 ( ( ( 1103 1117 phoP-activated phop-activated JJ 1118 1122 gene gene NN 1122 1123 ) ) ) 1124 1131 product product NN 1132 1134 is be VBZ 1135 1146 responsible responsible JJ 1147 1150 for for IN 1151 1159 defensin defensin NN 1160 1170 resistance resistance NN 1170 1171 . . . 1172 1174 We we PRP 1175 1179 also also RB 1180 1186 tested test VBD 1187 1190 for for IN 1191 1194 the the DT 1195 1202 ability ability NN 1203 1205 of of IN 1206 1215 defensins defensin NNS 1216 1220 NP-1 np-1 NN 1220 1221 , , , 1222 1226 NP-5 NP-5 NNP 1226 1227 , , , 1228 1231 and and CC 1232 1237 HNP-1 hnp-1 NN 1238 1240 to to TO 1241 1249 activate activate VB 1250 1253 pag pag NN 1254 1264 expression expression NN 1265 1268 and and CC 1269 1274 found find VBD 1275 1279 that that IN 1280 1285 these these DT 1286 1294 peptides peptide NNS 1295 1299 have have VBP 1300 1302 no no DT 1303 1309 effect effect NN 1309 1310 . . . 1311 1319 Defensin Defensin NNP 1320 1330 resistance resistance NN 1331 1333 is be VBZ 1334 1337 not not RB 1338 1341 the the DT 1342 1346 only only JJ 1347 1356 virulence virulence NN 1357 1371 characteristic characteristic JJ 1372 1382 controlled control VBN 1383 1385 by by IN 1386 1389 the the DT 1390 1399 PhoP-PhoQ PhoP-PhoQ NNP 1400 1407 regulon regulon NN 1408 1415 because because IN 1416 1425 mutations mutation NNS 1426 1428 in in IN 1429 1433 pagC pagc NN 1433 1434 , , , 1435 1437 as as RB 1438 1442 well well RB 1443 1445 as as IN 1446 1450 ones one NNS 1451 1453 in in IN 1454 1457 the the DT 1458 1462 phoP phop NN 1463 1468 locus locus NN 1469 1473 that that WDT 1474 1482 resulted result VBD 1483 1485 in in IN 1486 1498 constitutive constitutive JJ 1499 1502 pag pag NN 1503 1513 activation activation NN 1514 1515 ( ( ( 1515 1524 phenotype phenotype NN 1525 1530 PhoPc PhoPc NNP 1530 1531 ) ) ) 1531 1532 , , , 1533 1536 had have VBD 1537 1539 no no DT 1540 1546 effect effect NN 1547 1549 on on IN 1550 1558 defensin defensin NN 1559 1569 resistance resistance NN 1569 1570 , , , 1571 1575 even even RB 1576 1582 though though IN 1583 1587 they they PRP 1588 1596 rendered render VBD 1597 1600 the the DT 1601 1609 organism organism NN 1610 1619 avirulent avirulent JJ 1620 1623 and and CC 1624 1633 deficient deficient JJ 1634 1636 in in IN 1637 1645 survival survival NN 1646 1652 within within IN 1653 1664 macrophages macrophage NNS 1664 1665 . . . 1666 1669 The the DT 1670 1679 virulence virulence NN 1680 1686 defect defect NN 1687 1696 conferred confer VBN 1697 1699 by by IN 1700 1709 mutations mutation NNS 1710 1712 in in IN 1713 1716 the the DT 1717 1726 phoP-phoQ phop-phoq NN 1727 1740 two-component two-component JJ 1741 1751 regulatory regulatory JJ 1752 1758 system system NN 1759 1761 is be VBZ 1762 1765 not not RB 1766 1776 completely completely RB 1777 1786 explained explain VBN 1787 1789 by by IN 1790 1801 alterations alteration NNS 1802 1804 in in IN 1805 1815 resistance resistance NN 1816 1818 to to TO 1819 1827 cationic cationic JJ 1828 1836 proteins protein NNS 1837 1840 and and CC 1841 1849 involves involve VBZ 1850 1853 the the DT 1854 1861 control control NN 1862 1864 of of IN 1865 1870 other other JJ 1871 1879 proteins protein NNS 1880 1889 necessary necessary JJ 1890 1893 for for IN 1894 1896 S. S. NNP 1897 1908 typhimurium typhimurium NNP 1909 1917 survival survival NN 1918 1924 within within IN 1925 1936 macrophages macrophage NNS 1936 1937 . . .