Regulation of quorum-sensing in Vibrio cholerae

Walker, Lucas Maximilian ORCID: 0000-0001-8403-8687 (2022). Regulation of quorum-sensing in Vibrio cholerae. University of Birmingham. Ph.D.

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Abstract

Vibrio cholerae has spread across the world in seven recorded pandemics. Millions of recorded cases, and thousands of deaths, still occur world-wide each year. Survival of V. cholerae in the host and aquatic environments requires the careful regulation of gene expression. In part, this relies on quorum-sensing; a tool used by bacteria to respond to changes in population density. Two key transcription factors involved in the quorum-sensing cascade of V. cholerae are LuxO and HapR. Interestingly, the genes encoding these factors are highly variable amongst clinical isolates of pandemic cholera. Despite the importance of HapR and LuxO in escape from the host mucosa, natural competence, and expression of virulence factors, genome-wide DNA-binding targets have not yet been identified. Furthermore, it is not known how these proteins interact with other global regulators.

In this study, we assess the role of HapR and LuxO in pandemic V. cholerae. We show that mutations common in clinical isolates of V. cholerae abolish HapR expression. We determine DNA-binding targets of HapR and LuxO across the V. cholerae E7946 genome and identify genes with a diverse range of functions that are regulated by HapR. Additionally, we demonstrate how HapR and the cyclic AMP receptor protein (CRP) co-regulate transcription from the murQP promoter. Specifically, we show that these transcription factors bind DNA co-operatively.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):