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Bile dependent modulation of sensory transduction pathways in the enteric bacterium Vibrio cholerae

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Title Bile dependent modulation of sensory transduction pathways in the enteric bacterium Vibrio cholerae
 
Creator Ray, Sreejana
 
Subject Infectious Diseases and Immunology
 
Description Vibrio cholerae is a Gram negative, non invasive enteric pathogen and the etiologic agent of human diarrheal disease, cholera. It colonizes the small intestine and secretes the major toxin CT responsible for the disease symptoms. In V. cholerae expression of CT and several other
virulence factors are coordinately controlled by a hierarchical regulatory cascade known as ToxR regulon. The cascade starts with AphA and AphB which are responsible for transcriptional activation of a transmembrane transcription factor TcpP, which together with another transmembrane DNA-binding protein ToxR, activates expression of the master regulator toxT. ToxT then promotes the next level of the virulence cascade by activating ctxAB and tcpA. During
infection V. cholerae encounters bile, which is a heterogeneous mixture of salts and acids and required for lipid emulsification in the intestine. Several studies have indicated that the bile exerts pleiotropic effects on V. cholerae that affects virulence, motility, biofilm formation etc. This dissertation reports that bile induces a LysR type transcriptional regulator LeuO in V. cholerae and LeuO regulates expression of ToxR regulon. In the present study a differential proteomic analysis and transcriptional study identified that, LeuO was induced in V. cholera classical biotype O395 in presence of bile in the stationary phase of growth. In a ΔleuO mutant
expression of the ctxA, tcpA genes and the master virulence regulator toxT were induced in presence of bile at stationary phase of growth, indicating that LeuO negatively regulates V. cholerae virulence factors production under these conditions. ChIP and EMSA analysis demonstrated that LeuO directly binds at toxT promoter and act as a negative virulence regulator in V. cholerae. As H-NS, the global repressor was known to negatively regulate toxT expression
in V. cholerae, role of H-NS and LeuO were studied. Both ChIP and EMSA experiments confirmed that in a ΔleuO mutant H-NS cannot bind at toxT promoter in presence of bile at
stationary phase of growth. LeuO cooperatively binds at toxT promoter, share overlapping binding sites with H-NS and thereby it helps H-NS to bind at this promoter to negatively regulate the gene expression. Previously LeuO was known as a global H-NS antagonist in other enteric bacteria like E.coli, Salmonella enteric etc. But this study demonstrates a novel function of LeuO, rather than
acting as an H-NS antagonist, LeuO facilitates binding of H-NS to the toxT promoter and thereby regulates V. cholerae virulence at stationary phase of growth in presence of bile.
 
Date 2015
 
Type Thesis
NonPeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2566/1/Sreejana_Ray_PhD_Thesis.compressed.pdf
Ray, Sreejana (2015) Bile dependent modulation of sensory transduction pathways in the enteric bacterium Vibrio cholerae. PhD thesis, C U.
 
Relation http://www.eprints.iicb.res.in/2566/