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Decreased Potency of the Vibrio cholerae Sheathed Flagellum To Trigger Host Innate Immunity

Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Ave., Boston, Massachusetts 02115

Received 31 May 2007/ Returned for modification 31 July 2007/ Accepted 20 December 2007

Vibrio cholerae is a monoflagellated gram-negative bacterium that causes the severe diarrheal disease cholera. In contrast to Salmonella enterica serovar Typhimurium infection, which is accompanied by both acute diarrhea and high-level inflammation, V. cholerae infection is largely noninflammatory in human hosts. Bacterial flagella are composed of flagellin, a highly conserved protein that is also a target of the innate immune response. Because the V. cholerae flagellum is covered by a sheath, we hypothesized that it might be less prone to activation of the innate immune response than nonsheathed flagella, such as those produced by Salmonella serovar Typhimurium. Indeed, compared with Salmonella serovar Typhimurium flagella, V. cholerae flagella demonstrated significantly reduced NF-B activation in A549 human pulmonary epithelial cells. However, V. cholerae flagellin monomers, FlaD and FlaC, were almost equally potent with purified FliC, a monomer derived from Salmonella serovar Typhimurium flagella, in NF-B activation. Heat- and acid-induced dissociation assays showed that Salmonella serovar Typhimurium flagella disassembled far more readily into monomeric flagellins than V. cholerae flagella, suggesting that the differential levels of NF-B activation by V. cholerae and Salmonella serovar Typhimurium flagella are likely attributable to the difference in their flagellin shedding. Our results suggest that monomer dissociation of V. cholerae flagella is suppressed likely due to the presence of the sheath and that this unique structural feature of V. cholerae flagella may have evolved as a strategy to evade flagellin-triggered host innate immune responses in various host species.

Published ahead of print on 3 January 2008.

Editor: V. J. DiRita

^# Present address: Department of Microbiology and Immunology, University of Otago, P.O. Box 56, Dunedin, New Zealand.

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