The bacterium Vibrio cholerae (which causes the diarrheal disease cholera) secretes and detects signals that lead to the transcriptional repression of virulence genes by means of the regulator HapR; thus, its expression of virulence factors decreases with increased population density. Liu et al. used an antibiotic-coupled transposon screen to identify signals that might regulate virulence through this quorum-sensing pathway. Intriguingly, mutation of various genes involved in biosynthesis of V. cholerae’s flagellum decreased HapR activity and increased the production of virulence factors. Deletion of flgD, which encodes a flagellar rod protein, inhibited transcription of a hapR transcriptional reporter and that of a reporter activated by HapR, but promoted transcription of a reporter inhibited by HapR as well as production of virulence factors. Constitutive activation of the gene encoding FliA, which is involved in the activation of some flagellar genes, also promoted virulence factor production. Noting that FliA activity increases with the secretion of its inhibitor FlgM through the flagellar export apparatus, the authors determined that FlgM concentration was greater in supernatants from flgD mutant cultures than in those from wild-type cultures. Moreover, the effects of the flgD mutant on hapR expression were mediated through FliA. V. cholerae must traverse a layer of mucus to colonize intestinal epithelial cells, and both flagellar staining and electron microscopic analysis revealed that more than 80% of wild-type V. cholerae lost their flagellae while swimming through 1% mucin. The concentration of FlgM was higher in supernatants of cultures containing mucin, and hapR expression was decreased in mucin-exposed bacteria. Thus, the authors suggest that signals encountered en route to the epithelial cells may enable V. cholerae to jettison HapR-mediated repression of virulence at precisely the right time and place.
Z. Liu, T. Miyashiro, A. Tsou, A. Hsiao, M. Goulian, J. Zhu, Mucosal penetration primes Vibrio cholerae for host colonization by repressing quorum sensing. Proc. Natl. Acad. Sci. U.S.A. 105, 9769-9774 (2008). [Abstract] [Full Text]