{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T23:00:08Z","timestamp":1791068408853,"version":"4.1.0"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"20","license":[{"start":{"date-parts":[[2009,10,15]],"date-time":"2009-10-15T00:00:00Z","timestamp":1255564800000},"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":["J Bacteriol"],"published-print":{"date-parts":[[2009,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Francisella tularensis<\/jats:italic>\n            is an intracellular pathogen whose survival is in part dependent on its ability to resist the microbicidal activity of host-generated reactive oxygen species (ROS) and reactive nitrogen species (RNS). In numerous bacterial pathogens, CuZn-containing superoxide dismutases (SodC) are important virulence factors, localizing to the periplasm to offer protection from host-derived superoxide radicals (O\n            <jats:sub>2<\/jats:sub>\n            <jats:sup>\u2212<\/jats:sup>\n            ). In the present study, mutants of\n            <jats:italic>F<\/jats:italic>\n            .\n            <jats:italic>tularensis<\/jats:italic>\n            live vaccine strain (LVS) deficient in superoxide dismutases (SODs) were used to examine their role in defense against ROS\/RNS-mediated microbicidal activity of infected macrophages. An in-frame deletion\n            <jats:italic>F<\/jats:italic>\n            .\n            <jats:italic>tularensis<\/jats:italic>\n            mutant of\n            <jats:italic>sodC<\/jats:italic>\n            (\u0394\n            <jats:italic>sodC<\/jats:italic>\n            ) and a\n            <jats:italic>F<\/jats:italic>\n            .\n            <jats:italic>tularensis<\/jats:italic>\n            \u0394\n            <jats:italic>sodC<\/jats:italic>\n            mutant with attenuated Fe-superoxide dismutase (\n            <jats:italic>sodB<\/jats:italic>\n            ) gene expression (\n            <jats:italic>sodB<\/jats:italic>\n            \u0394\n            <jats:italic>sodC<\/jats:italic>\n            ) were constructed and evaluated for susceptibility to ROS and RNS in gamma interferon (IFN-\u03b3)-activated macrophages and a mouse model of respiratory tularemia. The\n            <jats:italic>F<\/jats:italic>\n            .\n            <jats:italic>tularensis<\/jats:italic>\n            \u0394\n            <jats:italic>sodC<\/jats:italic>\n            and\n            <jats:italic>sodB<\/jats:italic>\n            \u0394\n            <jats:italic>sodC<\/jats:italic>\n            mutants showed attenuated intramacrophage survival in IFN-\u03b3-activated macrophages compared to the wild-type\n            <jats:italic>F<\/jats:italic>\n            .\n            <jats:italic>tularensis<\/jats:italic>\n            LVS. Transcomplementing the\n            <jats:italic>sodC<\/jats:italic>\n            gene in the \u0394\n            <jats:italic>sodC<\/jats:italic>\n            mutant or inhibiting the IFN-\u03b3-dependent production of O\n            <jats:sub>2<\/jats:sub>\n            <jats:sup>\u2212<\/jats:sup>\n            or nitric oxide (NO) enhanced intramacrophage survival of the\n            <jats:italic>sod<\/jats:italic>\n            mutants. The \u0394\n            <jats:italic>sodC<\/jats:italic>\n            and\n            <jats:italic>sodB<\/jats:italic>\n            \u0394\n            <jats:italic>sodC<\/jats:italic>\n            mutants were also significantly attenuated for virulence in intranasally challenged C57BL\/6 mice compared to the wild-type\n            <jats:italic>F<\/jats:italic>\n            .\n            <jats:italic>tularensis<\/jats:italic>\n            LVS. As observed for macrophages, the virulence of the \u0394\n            <jats:italic>sodC<\/jats:italic>\n            mutant was restored in\n            <jats:italic>ifn<\/jats:italic>\n            -\u03b3\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            ,\n            <jats:italic>inos<\/jats:italic>\n            <jats:sup>\u2212<\/jats:sup>\n            <jats:sup>\/<\/jats:sup>\n            <jats:sup>\u2212<\/jats:sup>\n            , and\n            <jats:italic>phox<\/jats:italic>\n            <jats:sup>\u2212<\/jats:sup>\n            <jats:sup>\/<\/jats:sup>\n            <jats:sup>\u2212<\/jats:sup>\n            mice, indicating that SodC is required for resisting host-generated ROS. To conclude, this study demonstrates that SodB and SodC act to confer protection against host-derived oxidants and contribute to intramacrophage survival and virulence of\n            <jats:italic>F<\/jats:italic>\n            .\n            <jats:italic>tularensis<\/jats:italic>\n            in mice.\n          <\/jats:p>","DOI":"10.1128\/jb.00534-09","type":"journal-article","created":{"date-parts":[[2009,8,15]],"date-time":"2009-08-15T01:25:56Z","timestamp":1250299556000},"page":"6447-6456","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":61,"title":["Identification of\n            <i>Francisella tularensis<\/i>\n            Live Vaccine Strain CuZn Superoxide Dismutase as Critical for Resistance to Extracellularly Generated Reactive Oxygen Species"],"prefix":"10.1128","volume":"191","author":[{"given":"Amanda A.","family":"Melillo","sequence":"first","affiliation":[{"name":"Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York 12208"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manish","family":"Mahawar","sequence":"additional","affiliation":[{"name":"Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York 12208"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy J.","family":"Sellati","sequence":"additional","affiliation":[{"name":"Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York 12208"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meenakshi","family":"Malik","sequence":"additional","affiliation":[{"name":"Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York 12208"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis W.","family":"Metzger","sequence":"additional","affiliation":[{"name":"Center for Immunology and Microbial Disease, Albany Medical College, Albany, New York 12208"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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