[Seminar] The regulatory network coordinating natural transformation in the human pathogen Vibrio cholerae

Seminar

Title: The regulatory network coordinating natural transformation in the human pathogen Vibrio cholerae

Speaker: Brian Hammer

Affiliation: Georgia Institute of Technology, EUA

Host: Karina Xavier, Bacterial Signaling Lab

Abstract:

The bacterium Vibrio cholerae commonly forms biofilms on chitinous surfaces in marine environments, and can cause the fatal cholera diarrhea when ingested. Sequencing efforts suggest the mosaic genome structure of this bacterium resulted from rapid genetic exchange among Vibrios due to horizontal gene transfer (HGT). In V. cholerae reference strain C6706 isolated in 1991, multiple environmental cues promote natural transformation, one HGT mechanism, by inducing expression of regulator proteins that control transcription of genes for a DNA uptake apparatus. Quorum sensing (QS) signals stimulate production of the QS transcription factor HapR, chitin stimulates production of the TfoX regulator, and we recently identified the cytidine repressor CytR as an additional positive regulator of transformation. None of these three regulatory factors has been shown experimentally to bind to the promoter of any of the genes for the uptake apparatus. We recently reported that all sequenced V. cholerae isolates from the Haiti outbreak that began in 2010 are impaired for natural transformation despite conservation of known genes required for DNA uptake. Using computational analyses in conjunction with HGT assays, we are comparing
C6706 and Haiti strains to contemporary, sequenced V. cholerae isolates obtained from multiple locations including Nepal, the source of the Haiti outbreak. We predict that the mutation(s) that rendered the Haiti strains defective in natural transformation arose prior to introduction of V. cholerae to the island, and that our genomic and phylogenetic analyses will define the temporal origin and nature of the genetic defect(s). Complementary ChIP-seq and RNA-seq experiments in
C6706 are in progress to determine the genome-wide binding profile for each transformation regulator and the set of genes in the complex regulatory network linking QS, chitin and nucleosides to DNA uptake.
These studies will define new DNA uptake components, and the role that transformation plays in V. cholerae genome evolution.
 

www.hammerlab.biology.gatech.edu