{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:03:33Z","timestamp":1791162213859,"version":"4.1.0"},"reference-count":77,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,8,23]],"date-time":"2011-08-23T00:00:00Z","timestamp":1314057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>We demonstrate that disruption of the <jats:italic>htrA<\/jats:italic> (high temperature requirement A) gene in either the virulent <jats:italic>Bacillus anthracis<\/jats:italic> Vollum (pXO1<jats:sup>+<\/jats:sup>, pXO2<jats:sup>+<\/jats:sup>), or in the \u0394Vollum (pXO1<jats:sup>\u2010<\/jats:sup>, pXO2<jats:sup>\u2010<\/jats:sup>, nontoxinogenic and noncapsular) strains, affect significantly the ability of the resulting mutants to withstand heat, oxidative, ethanol and osmotic stress. The \u0394<jats:italic>htrA<\/jats:italic> mutants manifest altered secretion of several proteins, as well as complete silencing of the abundant extracellular starvation\u2010associated neutral protease A (NprA). Vollum\u0394<jats:italic>htrA<\/jats:italic> bacteria exhibit delayed proliferation in a macrophage infection assay, and despite their ability to synthesize the major <jats:italic>B.\u2003anthracis<\/jats:italic> toxins LT (lethal toxin) and ET (oedema toxin) as well as the capsule, show a decrease of over six orders of magnitude in virulence (lethal dose 50%\u2003=\u20033\u2003\u00d7\u200310<jats:sup>8<\/jats:sup> spores, in the guinea pig model of anthrax), as compared with the parental wild\u2010type strain. This unprecedented extent of loss of virulence in <jats:italic>B.\u2003anthracis,<\/jats:italic> as a consequence of deletion of a single gene, as well as all other phenotypic defects associated with <jats:italic>htr<\/jats:italic>A mutation, are restored in their corresponding trans\u2010complemented strains. It is suggested that the loss of virulence is due to increased susceptibility of the \u0394<jats:italic>htrA<\/jats:italic> bacteria to stress insults encountered in the host. On a practical note, it is demonstrated that the attenuated Vollum \u0394<jats:italic>htr<\/jats:italic>A is highly efficacious in protecting guinea pigs against a lethal anthrax challenge.<\/jats:p>","DOI":"10.1111\/j.1365-2958.2011.07790.x","type":"journal-article","created":{"date-parts":[[2011,8,1]],"date-time":"2011-08-01T10:15:47Z","timestamp":1312193747000},"page":"1542-1559","source":"Crossref","is-referenced-by-count":54,"title":["HtrA is a major virulence determinant of <i>Bacillus anthracis<\/i>"],"prefix":"10.1111","volume":"81","author":[{"given":"Theodor","family":"Chitlaru","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galia","family":"Zaide","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Ehrlich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itzhak","family":"Inbar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ofer","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avigdor","family":"Shafferman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,8,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03565.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.12.6817-6827.2002"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.8.4563-4579.2003"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2005.12.046"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.10.6923-6934.2005"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.5.2736-2743.2003"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03861.x"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.09.73"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200300575"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.188.10.3551-3571.2006"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.02029-06"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-90-481-9054-6_2"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00969.x"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00658-5"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3065"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.8.4549-4558.2000"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200700626"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2009.06.003"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01315-07"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00515-08"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.9.1183"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.184.20.5661-5671.2002"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01213-08"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2008.06483.x"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2009.07.001"},{"key":"e_1_2_6_27_1","first-page":"87","article-title":"Bacillus anthracis cell envelope components","volume":"271","author":"Fouet A.","year":"2002","journal-title":"Curr Top Microbiol Immunol"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2672.1999.00882.x"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2009.07.002"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.2.801-813.2003"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.04848.x"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00174-06"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1385\/1-59745-388-9:211"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2008.06460.x"},{"key":"e_1_2_6_35_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/j.1574-6968.1997.tb10242.x","article-title":"AtxA activates the transcription of genes harbored by both Bacillus anthracis virulence plasmids","volume":"15","author":"Guignot J.","year":"1997","journal-title":"FEMS Microbiol Lett"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.9.5538-5545.2001"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.61.080706.093445"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.24.7318-7328.2001"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2010.114"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02576.x"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.6.3584-3591.2004"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resmic.2009.08.017"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00925-10"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2009.06958.x"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2010.06.059"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.1994.tb00500.x"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00792-06"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2009.07.004"},{"key":"e_1_2_6_49_1","first-page":"62","article-title":"Structure and Function of Anthrax toxin","volume":"271","author":"Lacy T.M.","year":"2002","journal-title":"Curr Top Microbiol Immunol"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.10.3162"},{"key":"e_1_2_6_51_1","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1128\/iai.64.6.2088-2094.1996","article-title":"Construction and characterization of a Yersinia enterocolitica O:8 high\u2010temperature requirement (htrA) isogenic mutant","volume":"64","author":"Li S.\u2010R.","year":"1996","journal-title":"Infect Immun"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.186.1.164-178.2004"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.3.1618-1625.2004"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1159\/000225955"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2004.11.077"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1997.2941659.x"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.17.4473"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03345.x"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2003.10.053"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.2.654-663.2001"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1997.5601928.x"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2008.01.010"},{"key":"e_1_2_6_63_1","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1128\/iai.63.4.1369-1372.1995","article-title":"Protective immunity induced by Bacillus anthracis toxin\u2010deficient strains","volume":"63","author":"Pezard C.","year":"1995","journal-title":"Infect Immun"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.01757.x"},{"key":"e_1_2_6_65_1","first-page":"493","article-title":"A simple method of estimating fifty percent endpoints","volume":"27","author":"Reed L.J.","year":"1938","journal-title":"Am J Hyg"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.5.2888-2893.2001"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.1.563-572.2005"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.04887.x"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.00766-09"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-90-481-9054-6_32"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0710950105"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80743-6"},{"key":"e_1_2_6_73_1","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.68.2.207-233.2004"},{"key":"e_1_2_6_74_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1997.3041667.x"},{"key":"e_1_2_6_75_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2672.2005.02572.x"},{"key":"e_1_2_6_76_1","doi-asserted-by":"publisher","DOI":"10.1177\/1753425908100379"},{"key":"e_1_2_6_77_1","first-page":"179","volume-title":"Bacillus Anthracis and Anthrax","author":"Welkos S.L.","year":"2011"},{"key":"e_1_2_6_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00454-4"}],"container-title":["Molecular Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2958.2011.07790.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2958.2011.07790.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T03:43:25Z","timestamp":1697255005000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2958.2011.07790.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,8,23]]},"references-count":77,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2011,9]]}},"alternative-id":["10.1111\/j.1365-2958.2011.07790.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2958.2011.07790.x","archive":["Portico"],"relation":{},"ISSN":["0950-382X","1365-2958"],"issn-type":[{"value":"0950-382X","type":"print"},{"value":"1365-2958","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,8,23]]}}}