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Distant regulation of the Escherichia coli recombinase gene, fimB

Friar, Simon (2006) Distant regulation of the Escherichia coli recombinase gene, fimB. Doctor of Philosophy (PhD) thesis, University of Kent. (doi:10.22024/UniKent/01.02.94357) (KAR id:94357)

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Official URL:
https://doi.org/10.22024/UniKent/01.02.94357

Abstract

Escherichia coli is the archetypal member of the Enterobacteriaceae, and for many decades has been utilised as a model organism for the study of microbial genetics, biochemistry and molecular biology. The majority of isolates belong to the intestinal microflora of healthy humans and other mammals, although there are a number of patho-adapted isolates that cause both intestinal and extraintestinal diseases. Adherence to host cell receptors is a strategy employed by both commensal and pathogenic bacteria alike, and this is commonly achieved through the expression of cell surface adhesins that localise them at their preferred sites. Type 1 fimbriae are a particular adhesin that facilitate attachment of Escherichia coli to a number of mannose-containing cell-surface receptors within mammalian hosts. They are expressed by the majority (>80 %) of all E. coli isolates, commensal and pathogenic alike, and contribute to their colonisation and persistence at a number of different niches.

Expression of the type 1 fimbrial adhesin in Escherichia coli is phase variable. This reversible ON-OFF switching in expression is determined by the orientation of a 314 bp invertible element, which is catalysed by two recombinase proteins, FimB (switching in both directions) and FimE (switching predominantly from ON-to-OFF). The fimB recombinase gene is separated from the divergently transcribed nanC by a large (1.4 kb) intergenic region, and two regulatory proteins, NanR (Neu5Ac-responsive) and NagC (GlcNAc-responsive) bind to sequences far upstream (> 600 bp) of the fimB promoter to activate expression. Preliminary data had suggested that these regulatory proteins control fimB expression by an anti-repression mechanism that involves additional sequences proximal to nanC. In this study, I investigated the mechanism that determines distant activation of fimB by NanR and NagC. Contrary to previous findings, I provide evidence to suggest that nanC-proximal sequences do not inhibit fimB, and that a number of genetic elements are able to activate fimB expression at a distance. I show that NanR and NagC activate a single promoter for fimB from unusually large distances, and yet they do not appear to require additional, cA-active elements within the intervening sequence in order to function. The efficacy of activation by both these regulators is, however, sensitive to their precise location within the nanC-fimB intergenic region, and the significance of these data, with regards to a mechanism of activation is discussed.

Item Type: Thesis (Doctor of Philosophy (PhD))
DOI/Identification number: 10.22024/UniKent/01.02.94357
Additional information: This thesis has been digitised by EThOS, the British Library digitisation service, for purposes of preservation and dissemination. It was uploaded to KAR on 25 April 2022 in order to hold its content and record within University of Kent systems. It is available Open Access using a Creative Commons Attribution, Non-commercial, No Derivatives (https://creativecommons.org/licenses/by-nc-nd/4.0/) licence so that the thesis and its author, can benefit from opportunities for increased readership and citation. This was done in line with University of Kent policies (https://www.kent.ac.uk/is/strategy/docs/Kent%20Open%20Access%20policy.pdf). If you feel that your rights are compromised by open access to this thesis, or if you would like more information about its availability, please contact us at ResearchSupport@kent.ac.uk and we will seriously consider your claim under the terms of our Take-Down Policy (https://www.kent.ac.uk/is/regulations/library/kar-take-down-policy.html).
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Biosciences
SWORD Depositor: SWORD Copy
Depositing User: SWORD Copy
Date Deposited: 21 Jul 2022 14:52 UTC
Last Modified: 14 Jul 2023 09:29 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/94357 (The current URI for this page, for reference purposes)

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