Coordinated regulation of virulence by quorum sensing and motility pathways during the initial stages of Vibrio cholerae infection.

Pathogenic bacteria, such as Vibrio cholerae, must be capable of adapting to diverse living conditions, especially when transitioning from life in environmental reservoirs to life in a host. The abilities to sense arrival at a site suitable for colonization or infection and to respond with appropriate alterations in gene expression are crucial for a pathogen's success. Recently, we have shown that V. cholerae is able to recognize that it has reached its colonization site in the small intestine by sensing breakage of its flagellum as it penetrates the mucosal layer overlaying the intestinal epithelium. Flagellar loss results in the release of the anti-sigma factor FlgM and subsequent activation of the alternative sigma-factor FliA. FliA represses the quorum sensing-controlled transcriptional regulator, HapR, allowing increased expression of virulence factors such as Cholera Toxin (CT) and the Toxin Coregulated Pilus (TCP). In this way, the de-repression of virulence factor expression coincides with the arrival of bacteria at the site of infection at the intestinal mucosa. Our work reveals an interesting interplay between motility and quorum sensing signaling pathways to precisely time virulence gene expression during colonization.