Understanding the role of VpsT in Vibrio cholerae

Guest, Thomas ORCID: 0000-0002-7868-0611 (2021). Understanding the role of VpsT in Vibrio cholerae. University of Birmingham. Ph.D.

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Abstract

Cholera remains an important human pathogen despite the availability of vaccines and effective treatments. The current seventh pandemic is the longest recorded and outbreaks in Yemen have been the most deadly. The ability of Vibrio cholerae to shift between a human host and the aquatic environment has a vital role in its persistence. A complex transcriptional network reprograms the bacteria for life in cooler, nutrient poor environments.

In the aquatic environment V. cholerae uses a number of mechanisms to enhance its survival including formation of matrix- enclosed rugose phase variants, biofilm formation and colonisation of aquatic fauna. The transcriptional regulator VpsT, in response to the intracellular signalling molecule cyclic diguanylic acid (c-di-GMP), activates the expression of genes involved in the production of vibrio polysaccharide, promoting rugosity and the biofilm lifestyle. The regulator also represses expression of rpoS, the RNA polymerase sigma factor that co-ordinates the bacterial response to stress. However, the full repertoire of VpsT activity remains poorly defined.

To better understand the global regulatory role of VpsT we used chromatin immunoprecipitation, coupled with DNA sequencing, to map the distribution of VpsT across the genome. Our data identifies many additional targets for VpsT, substantially expanding the VpsT regulon. These targets include genes encoding proteins involved in motility, c-di-GMP metabolism and cell adhesion. Most notably, I show that VpsT is important for maintaining the correct level of c-di-GMP in the cell.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):