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Xenogeneic silencing-mediated temperature- and salinity-dependent regulation of type III secretion system 2 in Vibrio parahaemolyticus

Pratama, Andre 大阪大学

2022.03.24

概要

A marine bacterium Vibrio parahaemolyticus is a common seafood-borne pathogen that causes acute diarrhea in humans. A major virulence determinant of V. parahaemolyticus is a type III secretion system 2 (T3SS2) encoded on a pathogenicity island, Vp-PAI. The T3SS2 gene expression is affected by external environmental cues such as temperature and osmolarity. The expression is induced at 37°C and 0.1 M NaCl (a permissive condition) but is silenced at lower temperature or higher salinity (non-permissive conditions); however, the underlying mechanism remains elusive. Here, I show that histone-like nucleoid-structuring protein (H-NS), a xenogeneic silencing protein, regulates T3SS2 gene expression through transcriptional repression of a virulence regulator VtrB. Production of VtrB protein was abolished under the non-permissive conditions while production of its upstream regulator VtrA was consistent, and this repression was broken by the deletion of hns. I found that H-NS binding sites partially overlap with VtrA binding site within the vtrB promoter, which may block transcriptional activation of vtrB. H-NS suppresses its target genes by binding and multimerization to form filaments and/or bridges nucleoprotein complex. Mutations at dimerization domain of H-NS impaired repression of VtrB protein production in vivo but retains its binding ability to the vtrB promoter in vitro, suggesting that H-NS multimerization is crucial for VtrB repression. Together, these findings demonstrate that H-NS plays a pivotal role in the temperature- and salinity-dependent regulation of T3SS2, and expand our understanding of the virulence regulation in V. parahaemolyticus.

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