{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:13:50Z","timestamp":1785428030848,"version":"3.56.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"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":["mSphere"],"published-print":{"date-parts":[[2025,10,29]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Bile salts play a critical role in modulating the host gut. They possess antimicrobial properties wherein they disrupt the bacterial membrane and produce reactive oxygen species (ROS), causing DNA damage. Pathogens like\n                      <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                      regulate their metabolic activity to counteract the effects of bile. This study investigates the role of YqhD, an aldehyde reductase, in\n                      <jats:italic toggle=\"yes\">Salmonella\u2019<\/jats:italic>\n                      s bile salt susceptibility. Our findings reveal increased survival of the\n                      <jats:italic toggle=\"yes\">yqhD<\/jats:italic>\n                      mutant in the\n                      <jats:italic toggle=\"yes\">in-vitro<\/jats:italic>\n                      studies in LB media with bile, liver cell line HepG2 and C57BL\/6 mice on treatment with 8% sodium cholate in the cecum. Bile salts, physiologically produced for the digestion of fat, enhanced the organ burden of the\n                      <jats:italic toggle=\"yes\">yqhD<\/jats:italic>\n                      mutant in C57BL\/6 mice on replacing the chow diet with a high-fat diet (HFD). The\n                      <jats:italic toggle=\"yes\">yqhD<\/jats:italic>\n                      mutation, on bile salt exposure, also leads to increased ROS levels and modulation of antioxidant genes in the bacteria. The addition of the antioxidant glutathione during bile stress enhances the survival of STM WT and makes it similar to the survival of STM \u0394\n                      <jats:italic toggle=\"yes\">yqhD<\/jats:italic>\n                      . Similarly, in the\n                      <jats:italic toggle=\"yes\">\n                        gp91\n                        <jats:sup>\u2212\/\u2212phox<\/jats:sup>\n                      <\/jats:italic>\n                      mice, the organ burden and pathology of the liver and spleen were increased on STM WT infection, while it remained similar for the\n                      <jats:italic toggle=\"yes\">yqhD<\/jats:italic>\n                      mutant on exposure to HFD compared to that of chow-fed mice. Furthermore, the\n                      <jats:italic toggle=\"yes\">yqhD<\/jats:italic>\n                      mutant exhibited increased AcrAB efflux pump activity, regulated by RamA\/R regulon.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Foodborne pathogen\n                      <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                      can tolerate high concentrations of bile and even survive the harsh environment of the gall bladder. This study is significant as it explores the role of a novel antioxidant gene\n                      <jats:italic toggle=\"yes\">yqhD<\/jats:italic>\n                      in bile salt susceptibility of\n                      <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                      Typhimurium and Typhi. It highlights how the presence of gene\n                      <jats:italic toggle=\"yes\">yqhD<\/jats:italic>\n                      , though advantageous in macrophages, reduces the\n                      <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                      survival on bile salt exposure\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and in liver cell line HepG2. Deletion of\n                      <jats:italic toggle=\"yes\">yqhD<\/jats:italic>\n                      increased the survival on bile stress exposure, which was attributed to its ability to induce the AcrAB efflux pump of\n                      <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                      . A deeper understanding of how\n                      <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                      modulates gene expression in response to bile stress could provide valuable insights into addressing the chronic carriage of\n                      <jats:italic toggle=\"yes\">Salmonella<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00382-25","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T13:00:07Z","timestamp":1759410007000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["The resilience of\n                    <i>Salmonella<\/i>\n                    to bile stress is impaired due to the reduced efflux pump activity mediated by the antioxidant enzyme 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