Article

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

Departments of Microbiology, Physics, and Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 08/2008; 105(28):9769-74. DOI: 10.1073/pnas.0802241105
Source: PubMed

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.

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Available from: Zhi Liu, Aug 25, 2014
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    • "Stators also appear to sense viscosity changes for the Vibrio parahaemolyticus motor and respond by altering flagellation patterns[57]. For Proteus mirabilis, viscosity-dependent sensing appears to use the FliL protein (found in the flagellar basal body) to activate swarmer-cell differentiation[58], while V. cholera can lose their flagella while passing through the mucus glycocalyx, leading to downstream virulence gene expression[59]. Finally, the flagellum is a known mechanosensor for biofilm differentiation at infection sites, with pathways in Pseudomonas aeruginosa, V. cholera, V. parahaemolyticus and P. mirabilis well investigated and reviewed[60]. Similar to sensing for swarmer-cell differentiation, sensing for biofilm formation involves the function of the flagellar motor stators. "
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    • "HapR is a transcriptional regulator involved in quorum sensing in V. cholerae which also regulates expression of virulence genes. HapR represses expression of several virulence genes [101] and hapR expression is regulated by an unknown mechanism involving FliA [102]. hapR expression is depressed in flgM and flgD mutants (both of these mutations alleviate FlgM repression on FliA activity), while deletion of fliA results in elevated hapR expression [102]. "
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    • "Flagellar motility is an environmentally regulated behavior by which a bacterium propels itself through its surroundings , directed by behavior-modifying machinery such as the chemotaxis system (Adler 1966; Henrichsen 1972; reviewed in Macnab 1996; and McCarter 2006). Within the unique environments present in different host– microbe associations, both flagellar motility and the flagellum itself can play important roles in bacterial transit , niche specificity, effector secretion, biofilm formation, host recognition, and gene regulation (Young et al. 1999; Hayashi et al. 2001; Butler and Camilli 2004; Lemon et al. 2007; Liu et al. 2008). While the process of flagellar motility is difficult to study in most host–microbe interactions, the symbiosis between the bioluminescent, gram-negative bacterium Vibrio fischeri and its host the Hawaiian bobtail squid, Euprymna scolopes, is an ideal model in which to study how this critical behavior mediates symbiotic initiation. "
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