{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T02:36:38Z","timestamp":1788575798559,"version":"build-2803163510"},"reference-count":67,"publisher":"Microbiology Society","issue":"2","funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["R01AI073785"],"award-info":[{"award-number":["R01AI073785"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI126005"],"award-info":[{"award-number":["AI126005"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI118689"],"award-info":[{"award-number":["AI118689"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,1]]},"abstract":"<jats:p>In order to cause disease, pathogenic strains of <jats:italic>\n                     <jats:named-content content-type=\"species\">\n                        <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/doi.org\/10.1601\/nm.2947\" xlink:type=\"simple\">Vibrio cholerae<\/jats:ext-link>\n                     <\/jats:named-content>\n                  <\/jats:italic> rely on intricate regulatory networks to orchestrate the transition between their native aquatic environment and the human host. For example, bacteria in a nutrient-starved environment undergo a metabolic shift called the stringent response, which is mediated by the alarmone ppGpp and an RNA-polymerase binding transcriptional factor, DksA. In O1 serogroup strains of <jats:italic>V. cholerae,<\/jats:italic> which use the toxin co-regulated pilus (TCP) and cholera toxin (CT) as primary virulence factors, DksA was reported to have additional functions as a mediator of virulence gene expression. However, little is known about the regulatory networks coordinating virulence phenotypes in pathogenic strains that use TCP\/CT-independent virulence mechanisms. We therefore investigated whether functions of DksA outside of the stringent response are conserved in type three secretion system (T3SS)-positive <jats:italic>\n                     <jats:named-content content-type=\"species\">\n                        <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/doi.org\/10.1601\/nm.2947\" xlink:type=\"simple\">V. cholerae<\/jats:ext-link>\n                     <\/jats:named-content>\n                  <\/jats:italic>. In using the T3SS-positive clinically isolated O39 serogroup strain AM-19226, we observed an increase in <jats:italic>dksA<\/jats:italic> expression in the presence of bile at 37\u2009\u00b0C. However, DksA was not required for wild-type levels of T3SS structural gene expression, or for colonization <jats:italic>in vivo<\/jats:italic>. Rather, data indicate that DksA positively regulates the expression of master regulators in the motility hierarchy. Interestingly, the \u0394<jats:italic>dksA<\/jats:italic> strain forms a less robust biofilm than the WT parent strain at both 30 and 37 \u00b0C. We also found that DksA regulates the expression of <jats:italic>hapR<\/jats:italic>, encoding a major regulator of biofilm formation and protease expression. Athough DksA does not appear to modulate T3SS virulence factor expression, its activity is integrated into existing regulatory networks governing virulence-related phenotypes. Strain variations therefore may take advantage of conserved ancestral proteins to expand regulons responding to <jats:italic>in vivo<\/jats:italic> signals and thus coordinate multiple phenotypes important for infection.<\/jats:p>","DOI":"10.1099\/mic.0.001006","type":"journal-article","created":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T18:15:12Z","timestamp":1608228912000},"source":"Crossref","is-referenced-by-count":4,"title":["DksA coordinates bile-mediated regulation of virulence-associated phenotypes in type three secretion system-positive Vibrio cholerae"],"prefix":"10.1099","volume":"167","author":[{"given":"Madeline K.","family":"Sofia","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave., Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3960-0703","authenticated-orcid":false,"given":"Michelle","family":"Dziejman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Ave., Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.bbadis.2003.08.004","article-title":"Lipopolysaccharides of Vibrio cholerae. 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