TY - JOUR
T1 - Mucosal penetration primes Vibrio cholerae for host colonization by repressing quorum sensing
AU - Liu, Zhi
AU - Miyashiro, Tim
AU - Tsou, Amy
AU - Hsiao, Ansel
AU - Goulian, Mark
AU - Zhu, Jun
PY - 2008/7/15
Y1 - 2008/7/15
N2 - 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 σ-factor (σ 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-σ 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.
AB - 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 σ-factor (σ 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-σ 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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U2 - 10.1073/pnas.0802241105
DO - 10.1073/pnas.0802241105
M3 - Article
C2 - 18606988
AN - SCOPUS:47749105329
SN - 0027-8424
VL - 105
SP - 9769
EP - 9774
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 28
ER -