ToxR Antagonizes H-NS Regulation of Horizontally Acquired Genes to Drive Host Colonization

PLoS Pathogens

Shelley M. Payne¹  Aaron R. Conrado¹  Alexandra R. Mey¹  Misha I. Kazi¹  Bryan W. Davies² 

[1] Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, United States of America;Institute of Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas, United States of America

关键词: Gene regulation;    Vibrio cholerae;    Biofilms;    Sequence motif analysis;    Gene expression;    Promoter regions;    Regulator genes;    Transcription factors;   

DOI  :  10.1371/journal.ppat.1005570

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The virulence regulator ToxR initiates and coordinates gene expression needed by Vibrio cholerae to colonize the small intestine and cause disease. Despite its prominence in V. cholerae virulence, our understanding of the direct ToxR regulon is limited to four genes: toxT, ompT, ompU and ctxA. Here, we determine ToxR’s genome-wide DNA-binding profile and demonstrate that ToxR is a global regulator of both progenitor genome-encoded genes and horizontally acquired islands that encode V. cholerae’s major virulence factors and define pandemic lineages. We show that ToxR shares more than a third of its regulon with the histone-like nucleoid structuring protein H-NS, and antagonizes H-NS binding at shared binding locations. Importantly, we demonstrate that this regulatory interaction is the critical function of ToxR in V. cholerae colonization and biofilm formation. In the absence of H-NS, ToxR is no longer required for V. cholerae to colonize the infant mouse intestine or for robust biofilm formation. We further illustrate a dramatic difference in regulatory scope between ToxR and other prominent virulence regulators, despite similar predicted requirements for DNA binding. Our results suggest that factors in addition to primary DNA structure influence the ability of ToxR to recognize its target promoters.

【 授权许可】

CC BY