{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:37:31Z","timestamp":1790861851848,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2003,4,4]],"date-time":"2003-04-04T00:00:00Z","timestamp":1049414400000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2003,4]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The intracellular pathogen, <jats:italic>Salmonella enterica<\/jats:italic> serovar Typhimurium, is able to proliferate in phagocytes, although reactive oxygen and nitrogen intermediates are lethal to most phagocytosed bacteria. To determine whether repair of oxidatively damaged DNA is involved in <jats:italic>S. typhimurium<\/jats:italic> intramacrophage proliferation, null mutants of the DNA base excision repair (BER) system were generated. These mutants were deficient in discrete enzymes (<jats:italic>\u0394nth<\/jats:italic>, <jats:italic>\u0394nei<\/jats:italic>, <jats:italic>\u0394xth<\/jats:italic>, <jats:italic>\u0394nfo<\/jats:italic>) or in the defined glycosylase (<jats:italic>\u0394nth\/nei<\/jats:italic>) and endonuclease (<jats:italic>\u0394xth\/nfo<\/jats:italic>) steps. In this study, <jats:italic>S. typhimurium<\/jats:italic> BER mutants are characterized for the first time. <jats:italic>In vitro<\/jats:italic> characterization of the <jats:italic>Salmonella<\/jats:italic> BER mutants revealed phenotypes that are mostly consistent with characterized <jats:italic>Escherichia coli<\/jats:italic> BER mutants. These strains were used to evaluate the role of BER in the context of <jats:italic>Salmonella<\/jats:italic> virulence. <jats:italic>S. typhimurium \u0394xth<\/jats:italic> and <jats:italic>\u0394xth\/nfo<\/jats:italic> were significantly impaired for survival in both cultured and primary macrophages activated with interferon (IFN)\u2010\u03b3. Survival of <jats:italic>\u0394xth<\/jats:italic> and <jats:italic>\u0394xth\/nfo<\/jats:italic> was improved nearly to wild\u2010type levels in activated primary macrophages lacking both phagocyte oxidase and inducible nitric oxide synthase. In the murine typhoid fever model, <jats:italic>\u0394nth\/nei<\/jats:italic> was fivefold attenuated and <jats:italic>\u0394xth\/nfo<\/jats:italic> was 12\u2010fold attenuated compared with wild type. These data indicate that DNA oxidation is a mechanism that macrophages use to damage intracellular <jats:italic>Salmonella<\/jats:italic>, and suggest that BER\u2010mediated repair of this damage may be important in the establishment of <jats:italic>Salmonella<\/jats:italic> infection. We speculate that adaptation to a pathogenic lifestyle may influence the acquisition and retention of redundant BER enzymes.<\/jats:p>","DOI":"10.1046\/j.1365-2958.2003.03460.x","type":"journal-article","created":{"date-parts":[[2004,1,23]],"date-time":"2004-01-23T09:52:33Z","timestamp":1074851553000},"page":"549-559","source":"Crossref","is-referenced-by-count":50,"title":["The role of DNA base excision repair in the pathogenesis of <i>Salmonella enterica<\/i> serovar Typhimurium"],"prefix":"10.1111","volume":"48","author":[{"given":"Akamol E.","family":"Suvarnapunya","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. A. 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