{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:07:49Z","timestamp":1793138869643,"version":"4.5.0"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,2,5]]},"abstract":"<jats:p>\n                    To be successful pathogens, bacteria must often restrict the expression of virulence genes to host environments. This requires a physical or chemical marker of the host environment as well as a cognate bacterial system for sensing the presence of a host to appropriately time the activation of virulence. However, there have been remarkably few such signal\u2013sensor pairs identified, and the molecular mechanisms for host-sensing are virtually unknown. By directly applying a reporter strain of\n                    <jats:italic>Vibrio cholerae<\/jats:italic>\n                    , the causative agent of cholera, to a thin layer chromatography (TLC) plate containing mouse intestinal extracts, we found two host signals that activate virulence gene transcription. One of these was revealed to be the bile salt taurocholate. We then show that a set of bile salts cause dimerization of the transmembrane transcription factor TcpP by inducing intermolecular disulfide bonds between cysteine (C)-207 residues in its periplasmic domain. Various genetic and biochemical analyses led us to propose a model in which the other cysteine in the periplasmic domain, C218, forms an inhibitory intramolecular disulfide bond with C207 that must be isomerized to form the active C207\u2013C207 intermolecular bond. We then found bile salt\u2013dependent effects of these cysteine mutations on survival in vivo, correlating to our in vitro model. Our results are a demonstration of a mechanism for direct activation of the\n                    <jats:italic>V. cholerae<\/jats:italic>\n                    virulence cascade by a host signal molecule. They further provide a paradigm for recognition of the host environment in pathogenic bacteria through periplasmic cysteine oxidation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1218039110","type":"journal-article","created":{"date-parts":[[2013,1,23]],"date-time":"2013-01-23T02:27:25Z","timestamp":1358908045000},"page":"2348-2353","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":128,"title":["Bile salt\u2013induced intermolecular disulfide bond formation activates\n                    <i>Vibrio cholerae<\/i>\n                    virulence"],"prefix":"10.1073","volume":"110","author":[{"given":"Menghua","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"},{"name":"College of Animal Science and Technology, Zhejiang A and F University, Zhejiang 311300, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chambers","family":"Hughes","sequence":"additional","affiliation":[{"name":"Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Stern","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Nanjing Agricultural University, Nanjing 210095, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengtao","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Nanjing Agricultural University, Nanjing 210095, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biao","family":"Kan","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Beijing 102206, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Fenical","sequence":"additional","affiliation":[{"name":"Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California, San Diego, CA 92093;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104;"},{"name":"Department of Microbiology, Nanjing Agricultural University, Nanjing 210095, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,1,22]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90430-2"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.168.4.1487"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01094-07"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1369-5274(03)00032-8"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.1997.5481909.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1014640108"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00409-09"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0915021107"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01435-06"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1348-0421.1986.tb03037.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802241105"},{"key":"e_1_3_3_12_2","first-page":"24","article-title":"Bile acids: The good, the bad, and the ugly","volume":"14","author":"Hofmann AF","year":"1999","unstructured":"AF Hofmann, Bile acids: The good, the bad, and the ugly. 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