{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T18:21:36Z","timestamp":1782757296780,"version":"3.54.5"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,8,22]],"date-time":"2024-08-22T00:00:00Z","timestamp":1724284800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31602087"],"award-info":[{"award-number":["31602087"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32172857"],"award-info":[{"award-number":["32172857"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2024,8,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Ciprofloxacin-resistant\n              <jats:italic>Salmonella<\/jats:italic>\n              Typhimurium (\n              <jats:italic>S.<\/jats:italic>\n              Typhimurium) causes a significant health burden worldwide. A wealth of studies has been published on the contributions of different mechanisms to ciprofloxacin resistance in\n              <jats:italic>Salmonella<\/jats:italic>\n              spp. But we still lack a deep understanding of the physiological responses and genetic changes that underlie ciprofloxacin exposure. This study aims to know how phenotypic and genotypic characteristics are impacted by ciprofloxacin exposure, from ciprofloxacin-susceptible to ciprofloxacin-resistant strains\n              <jats:italic>in vitro<\/jats:italic>\n              . Here, we investigated the multistep evolution of resistance in replicate populations of\n              <jats:italic>S.<\/jats:italic>\n              Typhimurium during 24 days of continuously increasing ciprofloxacin exposure and assessed how ciprofloxacin impacts physiology and genetics. Numerous studies have demonstrated that RamA is a global transcriptional regulator that prominently perturbs the transcriptional landscape of\n              <jats:italic>S.<\/jats:italic>\n              Typhimurium, resulting in a ciprofloxacin-resistant phenotype appearing first; the quinolone resistance-determining region mutation site can only be detected later. Comparing the microbial physiological changes and RNA sequencing (RNA-Seq) results of ancestral and selectable mutant strains, the selectable mutant strains had some fitness costs, such as decreased virulence, an increase of biofilm-forming ability, a change of \u201ccollateral\u201d sensitivity to other drugs, and inability to utilize galactitol. Importantly, in the ciprofloxacin induced, RamA directly binds and activates the\n              <jats:italic>gatR<\/jats:italic>\n              gene responsible for the utilization of galactitol, but RamA deletion strains could not activate\n              <jats:italic>gatR<\/jats:italic>\n              . The elevated levels of RamA, which inhibit the galactitol metabolic pathway through the activation of\n              <jats:italic>gatR<\/jats:italic>\n              , can lead to a reduction in the growth rate, adhesion, and colonization resistance of\n              <jats:italic>S<\/jats:italic>\n              . Typhimurium. This finding is supported by studies conducted in M9 medium as well as\n              <jats:italic>in vivo<\/jats:italic>\n              infection models.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Treatment of antibiotic resistance can significantly benefit from a deeper understanding of the interactions between drugs and genetics. The physiological responses and genetic mechanisms in antibiotic-exposed bacteria are not well understood. Traditional resistance studies, often retrospective, fail to capture the entire resistance development process and typically exhibit unpredictable dynamics. To explore how clinical isolates of\n              <jats:italic>S.<\/jats:italic>\n              Typhimurium respond to ciprofloxacin, we analyzed their adaptive responses. We found that\n              <jats:italic>S.<\/jats:italic>\n              Typhimurium RamA-mediated regulation disrupts microbial metabolism under ciprofloxacin exposure, affecting genes in the galactitol metabolic pathways. This disruption facilitates adaptive responses to drug therapy and enhances the efficiency of intracellular survival. A more comprehensive and integrated understanding of these physiological and genetic changes is crucial for improving treatment outcomes.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/jb.00178-24","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T13:56:35Z","timestamp":1722434195000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["<i>Salmonella<\/i>\n            Typhimurium alters galactitol metabolism under ciprofloxacin treatment to balance resistance and virulence"],"prefix":"10.1128","volume":"206","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9639-6932","authenticated-orcid":true,"given":"Qiwei","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, College of Animal Medicine and Biosafety, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongfeng","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention, College of Animal Medicine and Biosafety, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9554-7102","authenticated-orcid":true,"given":"Yongchang","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Immunology and Pathogen Biology, Key Laboratory of Aging and Cancer Biology of Zhejiang Province, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Quan","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Animal Disease Control 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