{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:17:13Z","timestamp":1791505033394,"version":"4.3.4"},"reference-count":57,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI162944, R01AI172433"],"award-info":[{"award-number":["R01AI162944, R01AI172433"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI143704, R01GM130971"],"award-info":[{"award-number":["R01AI143704, R01GM130971"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005825","name":"National Institute of Food and Agriculture","doi-asserted-by":"publisher","award":["2020-67034-31750"],"award-info":[{"award-number":["2020-67034-31750"]}],"id":[{"id":"10.13039\/100005825","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,9,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      The human gut harbors enormous microbial diversity, which influences the gut\u2019s chemical environment. As the production of virulence factors affects bacterial fitness,\n                      <jats:italic toggle=\"yes\">Vibrio cholerae<\/jats:italic>\n                      has adapted to sense the gut chemical environment to selectively activate virulence factors at permissible intestinal niches. Here, we show that diffusible signal factors (DSFs) canonically used by gut proteobacteria for quorum-sensing communication can repress expression of essential ToxT-dependent virulence factors cholera toxin (\n                      <jats:italic toggle=\"yes\">ctxAB<\/jats:italic>\n                      ) and the toxin co-regulated pilus (\n                      <jats:italic toggle=\"yes\">tcpA-F<\/jats:italic>\n                      ). Unlike canonical quorum sensing, where DSFs are sensed by two-component systems or cyclic di-GMP-regulated proteins, DSFs target the central AraC-type transcriptional regulator ToxT. The most potent of these molecules is cis-2-hexadecenoic acid, which represses\n                      <jats:italic toggle=\"yes\">ctxAB<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">tcpA-F<\/jats:italic>\n                      expression by 84-fold and 12-fold, respectively. We find that the length of the carbon chain, the cis-2 double bond, and the carboxylic-acid terminus play important roles in the efficacy of these repressive chemicals. We further demonstrate that these chemicals interact with ToxT, preventing it from binding its target promoters while also rendering it susceptible to degradation. Our findings suggest that c2HDA targets ToxT\u2019s fatty acid-binding pocket, where high-affinity interactions likely maintain a restrained conformation that represses activity. Collectively, our data show that\n                      <jats:italic toggle=\"yes\">V. cholerae<\/jats:italic>\n                      senses interspecies DSF signals to regulate virulence activation, providing an opportunity to design interventions targeting the virulence of this pathogen.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">V. cholerae<\/jats:italic>\n                        continues to cause sporadic pandemics globally. Although cholera is a self-limiting acute disease, severe cases often require the use of antimicrobials in addition to rehydration therapy. Efforts to eradicate cholera have been hampered by the increased incidence of antimicrobial resistance and low vaccine coverage. The gut chemical environment, driven largely by the microbiota, has been shown to play important roles in modulating colonization by enteric pathogens. Pathogens utilize this chemical environment as cues to optimize virulence and survival. Understanding the underlying mechanisms of pathogen-microbiota interactions may therefore provide avenues to develop control measures targeting virulence and survival. Many of the mechanisms of pathogen-microbiota interactions have yet to be fully described. We demonstrate that\n                        <jats:italic toggle=\"yes\">V. cholerae<\/jats:italic>\n                        integrates interspecies chemical signals (DSFs) produced by members of the microbiota to regulate the expression of important virulence factors. DSFs potently repress the virulence island master regulator (ToxT), effectively attenuating cholera toxin secretion. As other related long-chain fatty acids have been reported to impair ToxT function, and as DSF producers localize to the intestinal crypts and mucus layer, it is likely that\n                        <jats:italic toggle=\"yes\">V. cholerae<\/jats:italic>\n                        employs these signals in a spatial-temporal manner to program the induction and repression of the energy-intensive virulence factors. Our work provides a framework for designing interventions to disrupt this virulence and survival program to control this pathogen.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01537-25","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T13:01:27Z","timestamp":1753966887000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["<i>Vibrio cholerae<\/i>\n                    integrates interspecies quorum-sensing signals to regulate virulence"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1804-244X","authenticated-orcid":true,"given":"Erick Maosa","family":"Bosire","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05bnh6r87","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University","place":["Ithaca, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myfanwy C.","family":"Adams","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05bnh6r87","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Medicine, College of Veterinary Medicine, Cornell University","place":["Ithaca, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina D.","family":"Pavinski Bitar","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05bnh6r87","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University","place":["Ithaca, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon G.","family":"Murphy","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05bnh6r87","id-type":"ROR","asserted-by":"publisher"}],"name":"Weill Institute for Cell and Molecular Biology, Cornell University","place":["Ithaca, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Ho","family":"Shin","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05bnh6r87","id-type":"ROR","asserted-by":"publisher"}],"name":"Weill Institute for Cell and Molecular Biology, Cornell University","place":["Ithaca, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5733-7275","authenticated-orcid":false,"given":"Joshua S.","family":"Chappie","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05bnh6r87","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Molecular Medicine, College of Veterinary Medicine, Cornell University","place":["Ithaca, USA"]},{"name":"USDA-ARS Soil Management and Sugarbeet Research Unit, Crops Research Laboratory","place":["Fort Collins, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3283-9161","authenticated-orcid":true,"given":"Tobias","family":"D\u00f6rr","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05bnh6r87","id-type":"ROR","asserted-by":"publisher"}],"name":"Weill Institute for Cell and Molecular Biology, Cornell University","place":["Ithaca, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3740-9163","authenticated-orcid":false,"given":"Craig","family":"Altier","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05bnh6r87","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University","place":["Ithaca, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2024.05.002"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-015-1141-5"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2022.05.009"},{"key":"e_1_3_3_5_2","first-page":"201","article-title":"The complexity of ToxT-dependent transcription in Vibrio cholerae","volume":"133","author":"Weber GG","year":"2011","unstructured":"Weber GG, Klose KE. 2011. 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