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Title: Distant regulation of the Escherichia coli recombinase gene, FimB
Author: Friar, Simon
ISNI:       0000 0004 2669 3335
Awarding Body: University of Kent
Current Institution: University of Kent
Date of Award: 2006
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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.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Q Science