{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T21:37:11Z","timestamp":1789162631034,"version":"build-2803163510"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2003,12,1]],"date-time":"2003-12-01T00:00:00Z","timestamp":1070236800000},"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":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2003,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Mutants\nof\n            <jats:italic>Salmonella enterica<\/jats:italic>\n            serovar Typhimurium resistant to\nfusidic acid (Fus\n            <jats:sup>r<\/jats:sup>\n            ) have mutations in\n            <jats:italic>fusA<\/jats:italic>\n            , the\ngene encoding translation elongation factor G (EF-G). Most\nFus\n            <jats:sup>r<\/jats:sup>\n            mutants have reduced fitness in vitro and in vivo, in\npart explained by mutant EF-G slowing the rate of protein synthesis and\ngrowth. However, some Fus\n            <jats:sup>r<\/jats:sup>\n            mutants with normal rates of\nprotein synthesis still suffer from reduced fitness in vivo. As shown\nhere, Fus\n            <jats:sup>r<\/jats:sup>\n            mutants could be similarly ranked in their\nrelative fitness in mouse infection models, in a macrophage infection\nmodel, in their relative hypersensitivity to hydrogen peroxide in vivo\nand in vitro, and in the amount of RpoS production induced upon entry\ninto the stationary phase. We identify a reduced ability to induce\nproduction of RpoS (\u03c3\n            <jats:sup>s<\/jats:sup>\n            ) as a defect associated with\nFus\n            <jats:sup>r<\/jats:sup>\n            strains. Because RpoS is a regulator of the general\nstress response, and an important virulence factor in\n            <jats:italic>Salmonella<\/jats:italic>\n            , an inability to produce RpoS in appropriate\namounts can explain the low fitness of Fus\n            <jats:sup>r<\/jats:sup>\n            strains in vivo.\nThe unfit Fus\n            <jats:sup>r<\/jats:sup>\n            mutants also produce reduced levels of the\nregulatory molecule ppGpp in response to starvation. Because ppGpp is a\npositive regulator of RpoS production, we suggest that a possible cause\nof the reduced levels of RpoS is the reduction in ppGpp production\nassociated with mutant EF-G. The low fitness of Fus\n            <jats:sup>r<\/jats:sup>\n            mutants\nin vivo suggests that drugs that can alter the levels of global\nregulators of gene expression deserve attention as potential\nantimicrobial\nagents.\n          <\/jats:p>","DOI":"10.1128\/aac.47.12.3743-3749.2003","type":"journal-article","created":{"date-parts":[[2003,11,24]],"date-time":"2003-11-24T22:53:35Z","timestamp":1069714415000},"page":"3743-3749","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":39,"title":["FusidicAcid-Resistant Mutants of\n            <i>Salmonella enterica<\/i>\n            SerovarTyphimurium with Low Fitness In Vivo Are Defective in RpoSInduction"],"prefix":"10.1128","volume":"47","author":[{"given":"Mirjana","family":"Macvanin","sequence":"first","affiliation":[{"name":"Department\rof Cell and Molecular Biology, The Biomedical Center, Uppsala\rUniversity, S-751 24\rUppsala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Bjo\u0308rkman","sequence":"additional","affiliation":[{"name":"Department of Bacteriology,\rSwedish Institute for Infectious Disease Control, S-171 82\rSolna"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Microbiology and\rTumour Biology Center, The Karolinska Institute, S-171 77\rStockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikael","family":"Rhen","sequence":"additional","affiliation":[{"name":"Microbiology and\rTumour Biology Center, The Karolinska Institute, S-171 77\rStockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan I.","family":"Andersson","sequence":"additional","affiliation":[{"name":"Department of Bacteriology,\rSwedish Institute for Infectious Disease Control, S-171 82\rSolna"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diarmaid","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department\rof Cell and Molecular Biology, The Biomedical Center, Uppsala\rUniversity, S-751 24\rUppsala"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1998.1779"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.3949"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5457.1479"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1999.01142.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)34138-3"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.178.13.3763-3770.1996"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.184.16.4455-4465.2002"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117750"},{"key":"e_1_3_2_10_2","unstructured":"Cashel M. 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