{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T22:40:30Z","timestamp":1783636830572,"version":"3.55.0"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2009,2,1]],"date-time":"2009-02-01T00:00:00Z","timestamp":1233446400000},"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":[[2009,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Complicated urinary tract infections (UTI) caused by\n            <jats:italic>Proteus mirabilis<\/jats:italic>\n            are associated with severe pathology in the bladder and kidney. To investigate the roles of two established cytotoxins, the HpmA hemolysin, a secreted cytotoxin, and proteus toxic agglutinin (Pta), a surface-associated cytotoxin, mutant analysis was used in conjunction with a mouse model of ascending UTI. Inactivation of\n            <jats:italic>pta<\/jats:italic>\n            , but not inactivation of\n            <jats:italic>hpmA<\/jats:italic>\n            , resulted in significant decreases in the bacterial loads of the mutant in kidneys (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.01) and spleens (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05) compared to the bacterial loads of the wild type; the 50% infective dose (ID\n            <jats:sub>50<\/jats:sub>\n            ) of an isogenic\n            <jats:italic>pta<\/jats:italic>\n            mutant or\n            <jats:italic>hpmA pta<\/jats:italic>\n            double mutant was 100-fold higher (5 \u00d7 10\n            <jats:sup>8<\/jats:sup>\n            CFU) than the ID\n            <jats:sub>50<\/jats:sub>\n            of parent strain HI4320 (5 \u00d7 10\n            <jats:sup>6<\/jats:sup>\n            CFU). Colonization by the parent strain caused severe cystitis and interstitial nephritis as determined by histopathological examination. Mice infected with the same bacterial load of the\n            <jats:italic>hpmA pta<\/jats:italic>\n            double mutant showed significantly reduced pathology (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.01), suggesting that the additive effect of these two cytotoxins is critical during\n            <jats:italic>Proteus<\/jats:italic>\n            infection. Since Pta is surface associated and important for the persistence of\n            <jats:italic>P. mirabilis<\/jats:italic>\n            in the host, it was selected as a vaccine candidate. Mice intranasally vaccinated with a site-directed (indicated by an asterisk) (S366A) mutant purified intact toxin (Pta*) or the passenger domain Pta-\u03b1*, each independently conjugated with cholera toxin (CT), had significantly lower bacterial counts in their kidneys (\n            <jats:italic>P<\/jats:italic>\n            = 0.001) and spleens (\n            <jats:italic>P =<\/jats:italic>\n            0.002) than mice that received CT alone. The serum immunoglobulin G levels correlated with protection (\n            <jats:italic>P<\/jats:italic>\n            = 0.03). This is the first report describing the in vivo cytotoxicity and antigenicity of an autotransporter in\n            <jats:italic>P. mirabilis<\/jats:italic>\n            and its use in vaccine development.\n          <\/jats:p>","DOI":"10.1128\/iai.01050-08","type":"journal-article","created":{"date-parts":[[2008,11,25]],"date-time":"2008-11-25T01:50:29Z","timestamp":1227577829000},"page":"632-641","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":59,"title":["Vaccination with Proteus Toxic Agglutinin, a Hemolysin-Independent Cytotoxin In Vivo, Protects against\n            <i>Proteus mirabilis<\/i>\n            Urinary Tract Infection"],"prefix":"10.1128","volume":"77","author":[{"given":"Praveen","family":"Alamuri","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn A.","family":"Eaton","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology"},{"name":"Unit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie D.","family":"Himpsl","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara N.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology"},{"name":"Unit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry L. 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