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 -factor ( 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-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.

Reactogenicity of live-attenuated Vibrio cholerae vaccines is dependent on flagellins

“…Thus, V. cholerae does not appear to depend on flagellar-based motility for spread within intestinal sites in this model. Flagella-independent motility has been observed for V. cholerae (26,27), although the precise mechanism(s) underlying this process has not been identified.…”

The VarS/VarA two-component system modulates the activity of the Vibrio cholerae quorum-sensing transcriptional regulator HapR

“…FliA represses HapR expression, and thus the motility pathway works in conjunction with the quorum-sensing pathway to maximally repress HapR expression during the initial stages of colonization, when cell density is low. This repression of HapR allows for maximal expression of virulence genes early in the infectious cycle (Liu et al, 2008). Additionally, HapR is regulated by VqmA, which is thought to respond to an as-yet-unidentified environmental signal .…”

Bacterial Wheel Locks: Extracellular Polysaccharide Inhibits Flagellar Rotation

“…The peritrichous flagella of Vibrio parahaemolyticus sense surface contact, globally altering gene expression (10). Likewise, breaking of the flagella of V. cholerae during transit of the thick mucus layer blanketing epithelial cells induces a genetic regulatory pathway that increases virulence factor production (11). Contact of a surface in Caulobacter crescentus stimulates synthesis of the polysaccharide holdfast structure, and it is thought that inhibition of flagellar rotation is key to this signaling process (12).…”