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Understanding the regulation of acid resistance in E. coli using whole genome techniques

Johnson, Matthew David (2011)
Ph.D. thesis, University of Birmingham.

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The ability of bacteria to thrive in a variety of host environments depends on their capacity to sense and respond to a wide array of stressors. E. coli encounters many stresses during transit through the gastro-intestinal tract, including acid stress. Acid stress response in E. coli is regulated by a complex network called AR2. The AR2 network comprises several local regulators that collate signals from multiple two-component systems (TCS) including RcsBD, EvgAS and PhoPQ.

We combined lab-based evolution and whole genome re-sequencing to generate and identify mutations that confer increased acid resistance in E. coli K-12. All of these mutations map in the gene encoding EvgS, the sensor kinase of the EvgAS TCS. Using a luciferase reporter system and phenotypic assays we characterised the nature of these evgS mutations and their contribution to acid resistance. We also used high-temporal resolution luciferase reporter assays to uncover novel aspects of this network and implicate PhoP in the repression of acid resistance. Finally, we used our evgS mutants to characterise novel interactions within the AR2 network between the two component systems RcsBD and EvgAS. These results are discussed in relation to the role of regulatory networks in bacteria.

Type of Work:Ph.D. thesis.
Supervisor(s):Lund, Peter A.
School/Faculty:Colleges (2008 onwards) > College of Life & Environmental Sciences
Department:School of Biosciences
Subjects:QR Microbiology
Institution:University of Birmingham
ID Code:3006
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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