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PNAS 105 (28): 9769-9774

Copyright © 2008 by the National Academy of Sciences.

BIOLOGICAL SCIENCES / MICROBIOLOGY

Mucosal penetration primes Vibrio cholerae for host colonization by repressing quorum sensing

Zhi Liu*, Tim Miyashiro{dagger}, Amy Tsou*, Ansel Hsiao*, Mark Goulian{dagger},{ddagger}, and Jun Zhu*,{ddagger},§

Departments of *Microbiology, {dagger}Physics, and {ddagger}Biology, University of Pennsylvania, Philadelphia, PA 19104

Edited by R. John Collier, Harvard Medical School, Boston, MA, and approved April 17, 2008

Received for publication March 7, 2008.

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.

Author contributions: Z.L., T.M., A.H., M.G., and J.Z. designed research; Z.L., T.M., A.T., A.H., and J.Z. performed research; M.G. contributed new reagents/analytic tools; Z.L., T.M., M.G., and J.Z. analyzed data; and Z.L., T.M., A.H., and J.Z. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/cgi/content/full/0802241105/DCSupplemental.

§To whom correspondence should be addressed. E-mail: junzhu{at}mail.med.upenn.edu

© 2008 by The National Academy of Sciences of the USA

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