Global gene expression in ETEC H10407

Sharma, Prateek (2017). Global gene expression in ETEC H10407. University of Birmingham. Ph.D.

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Abstract

Enterotoxigenic Escherichia coli is a gram negative bacterium that is responsible for acute watery diarrhoea in humans. Virulence factors of ETEC have been characterized but underlying gene regulatory mechanisms are not yet understood. Moreover, antibiotic resistance in bacteria is a serious problem worldwide. Multiple antibiotic resistance in bacteria can be driven by transcriptional regulators in the AraC/XylS family. The E. coli mar regulon is considered a paradigm for such
systems. The mar locus consists of 3 genes; marR, marA, and marE. A transcriptional activator encoded by marA enhances drug resistance by binding to "marbox" sequences at target promoters. The best characterised MarA targets encode the AcrAB-TolC drug efflux pump.
In this work, we have defined a molecular mechanism controlling expression of ETEC heat stable enterotoxin. We show that the CRP directly activates expression of heat-stable toxin and H-NS can exclude CRP from the activation-binding site. We also show that heat-stable toxin expression can be controlled by osmo-metabolic flux; CRP and H-NS allow the toxin gene promoter to respond to both glucose and salt. These conditions are encountered on host cell attachment and during oral rehydration therapy. We also identify 33 MarA targets to reveal novel mechanisms of antibiotic resistance.

Type of Work:	Thesis (Doctorates > Ph.D.)
Award Type:	Doctorates > Ph.D.
Supervisor(s):	Supervisor(s) Email ORCID Grainger, David UNSPECIFIED UNSPECIFIED
Licence:
College/Faculty:	Colleges (2008 onwards) > College of Life & Environmental Sciences
School or Department:	School of Biosciences
Funders:	Other
Other Funders:	The Darwin Trust of Edinburgh
Subjects:	Q Science > QR Microbiology
URI:	http://etheses.bham.ac.uk/id/eprint/7918

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