{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T23:44:59Z","timestamp":1787701499986,"version":"build-2784847793"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2012,8,1]],"date-time":"2012-08-01T00:00:00Z","timestamp":1343779200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The virulence of\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Bacillus anthraci<\/jats:named-content>\n                    s, the causative agent of anthrax, stems from its antiphagocytic capsule, encoded by pXO2, and the tripartite toxins encoded by pXO1. The accepted paradigm states that anthrax is both an invasive and toxinogenic disease and that the toxins play major roles in pathogenicity. We tested this assumption by a systematic study of mutants with combined deletions of the\n                    <jats:italic>pag<\/jats:italic>\n                    ,\n                    <jats:italic>lef<\/jats:italic>\n                    , and\n                    <jats:italic>cya<\/jats:italic>\n                    genes, encoding protective antigen (PA), lethal factor (LF), and edema factor (EF), respectively. The resulting seven mutants (single, double, and triple) were evaluated following subcutaneous (s.c.) and intranasal (i.n.) inoculation in rabbits and guinea pigs. In the rabbit model, virulence is completely dependent on the presence of PA. Any mutant bearing a\n                    <jats:italic>pag<\/jats:italic>\n                    deletion behaved like a pXO1-cured mutant, exhibiting complete loss of virulence with attenuation indices of over 2,500,000 or 1,250 in the s.c. or i.n. route of infection, respectively. In marked contrast, in guinea pigs, deletion of\n                    <jats:italic>pag<\/jats:italic>\n                    or even of all three toxin components resulted in relatively moderate attenuation, whereas the pXO1-cured bacteria showed complete attenuation. The results indicate that a pXO1-encoded factor(s), other than the toxins, has a major contribution to the virulence mechanism of\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. anthracis<\/jats:named-content>\n                    in the guinea pig model. These unexpected toxin-dependent and toxin-independent manifestations of pathogenicity in different animal models emphasize the importance and need for a comprehensive evaluation of\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">B. anthracis<\/jats:named-content>\n                    virulence in general and in particular for the design of relevant next-generation anthrax vaccines.\n                  <\/jats:p>","DOI":"10.1128\/iai.00244-12","type":"journal-article","created":{"date-parts":[[2012,5,15]],"date-time":"2012-05-15T02:42:58Z","timestamp":1337049778000},"page":"2623-2631","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":48,"title":["Differential Contribution of Bacillus anthracis Toxins to Pathogenicity in Two Animal Models"],"prefix":"10.1128","volume":"80","author":[{"given":"Haim","family":"Levy","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shay","family":"Weiss","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeev","family":"Altboum","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef","family":"Schlomovitz","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Itai","family":"Glinert","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assa","family":"Sittner","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avigdor","family":"Shafferman","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kobiler","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.12.6817-6827.2002"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.5.2736-2743.2003"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00647-08"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2010.00969.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2011.07790.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.188.10.3551-3571.2006"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.02029-06"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.09.73"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.8.4549-4558.2000"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2009.06.003"},{"key":"e_1_3_2_12_2","first-page":"2523","article-title":"Noninvasive imaging technologies reveal edema toxin as key virulence factor in anthrax","volume":"178","author":"Dumetz F","year":"2011","unstructured":"DumetzF. 2011. Noninvasive imaging technologies reveal edema toxin as key virulence factor in anthrax. Biophys. Imaging Comput. Biol. 178:2523\u20132535.","journal-title":"Biophys. Imaging Comput. Biol."},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00006-11"},{"key":"e_1_3_2_14_2","unstructured":"FDA. 16 November 2010. 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