Species-specific quorum sensing represses the chitobiose utilization locus in Vibrio cholerae

The marine facultative pathogen Vibrio cholerae forms complex multicellular communities called biofilms on the shells of crustacean zooplankton in its aquatic reservoir. These shells are primarily composed of the polysaccharide chitin. V. cholerae-chitin interactions are critical for the growth, evolution, and waterborne transmission of cholera. This is due, in part, to chitin inducing changes in gene expression in this pathogen. Here, we sought to identify factors that influence chitin-induced expression of one locus, the chitobiose utilization operon (chb), which is required for the uptake and catabolism of the chitin disaccharide. Through a series of genetic screens, we identified that the master regulator of quorum sensing, HapR, is likely a direct repressor of the chb operon. We also found that the levels of HapR in V. cholerae are regulated by the ClpAP protease. Furthermore, we show that the canonical quorum sensing cascade in V. cholerae regulates chb expression in a HapR-dependent manner. Through this analysis we found that signaling via the species-specific autoinducer CAI-1, but not the inter-species autoinducer AI-2, influences chb expression. This phenomenon of species-specific regulation may enhance the fitness of this pathogen in its environmental niche.