The cAMP receptor protein controls \(Vibrio\) \(cholerae\) gene expression in response to host colonisation

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Roussel, Jainaba (2018). The cAMP receptor protein controls \(Vibrio\) \(cholerae\) gene expression in response to host colonisation. University of Birmingham. Ph.D.

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Abstract

The bacterium Vibrio cholerae is the causative agent of the acute diarrhoeal disease cholera. V. cholerae is naturally found in aquatic environments but can switch lifestyles to cause disease in humans. The lifestyle switch requires modulation of genetic systems. Much of the regulation occurs at the level of gene expression and is controlled by transcription factors. In this work, I show that the global transcription regulator, cAMP receptor protein (CRP), plays an integral role in the regulatory network that controls lifestyle switching. I have identified two sites for CRP in the intergenic region between rtxHCA and rtxBDE, a locus which encodes the multifunctional-autoprocessing repeats-in-toxin (MARTX) toxin and toxin transport system respectively. Using a combination of genetics, biochemistry and in vivo animal studies, I have determined a CRP dependent regulation of gene expression for toxin transport in response to host infection. This work shows that rtxHCA is constitutively expressed and not subject to regulation by CRP whist CRP acts as a repressor of rtxBDE transcription. Examination of further CRP targeted genes reveals similar behaviour upon host colonisation. These findings suggest that toxin export occurs in nutritionally rich environments, where the MARTX toxin can exert cytopathic and cytotoxic effects on host cells.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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