The purpose of this project is to continue work from the DEFRA funded project OD2007, which identified the phenomenon of antibiotic resistance gene silencing in bacteria, i.e. shutting off expression of otherwise functional gene systems (described below in further detail). This is, to our knowledge, the first time that silencing of antibiotic resistance genes has been demonstrated, a phenomenon that is of considerable scientific interest and potentially of great practical importance. It is most likely that silencing arises due to a novel gene control mechanism, the characterisation of which has obvious scientific merit. However, from medical and veterinary contexts, characterisation of gene silencing is imperative, because bacteria carrying silent resistance genes represent a previously unknown and unquantified threat and because it may be possible to harness the mechanism to counter the current threat of multiple antibiotic resistance.<P> It is important, therefore, to characterise the molecular mechanism by which silencing operates and to determine if it operates in bacterial species other than Escherichia coli. Prior studies have indicated that an uncharacterised mutation(s) in the genome of E. coli 345-2 (the study strain) results, directly or indirectly, in gene silencing.
The primary objectives of this proposal are, therefore:
<OL> <LI> To identify the locus responsible for resistance gene silencing
<LI> To characterise the silencing mechanism
<LI> To determine if gene silencing confers a selective growth/survival advantage
<LI> To determine if antibiotic resistance gene silencing can occur in other species