title: Mucosal penetration primes Vibrio cholerae for host colonization by repressing quorum sensing.
abstract: To successfully infect a host and cause the diarrheal disease cholera, Vibrio cholerae must penetrate the intestinal mucosal layer and express virulence genes. Previous studies have demonstrated that the transcriptional regulator HapR, which is part of the quorum sensing network in V. cholerae, represses the expression of virulence genes. Here, we show that hapR expression is also modulated by the regulatory network that governs flagellar assembly. Specifically, FliA, which is the alternative sigma-factor (sigma(28)) that activates late-class flagellin genes in V. cholerae, represses hapR expression. In addition, we show that mucin penetration by V. cholerae is sufficient to break flagella and so cause the secretion of FlgM, the anti-sigma factor that inhibits FliA activity. During initial colonization of host intestinal tissue, hapR expression is repressed because of low cell density. However, full repression of hapR expression does not occur in fliA mutants, which results in attenuated colonization. Our results suggest that V. cholerae uses flagellar machinery to sense particular intestinal signals before colonization and enhance the expression of virulence genes by modulating the output of quorum sensing signaling.
authors.affiliation: Departments of Microbiology, Physics, and Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liu
authors.forename: Tim
authors.initials: T
authors.lastname: Miyashiro
authors.forename: Amy
authors.initials: A
authors.lastname: Tsou
authors.forename: Ansel
authors.initials: A
authors.lastname: Hsiao
authors.forename: Mark
authors.initials: M
authors.lastname: Goulian
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology; D002771:Cholera / Q000209:etiology; D005407:Flagella; D015964:Gene Expression Regulation, Bacterial; D007413:Intestinal Mucosa / Q000382:microbiology*; D053038:Quorum Sensing; D012097:Repressor Proteins / Q000502:physiology*; D014734:Vibrio cholerae / Q000472:pathogenicity*; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D012097:Repressor Proteins