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Beta-lactam resistance in Campylobacter

Stones, Leanne (2011)
Ph.D. thesis, University of Birmingham.

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Abstract

Resistance to β-lactam antibiotics in Campylobacter is often associated with the production of a β-lactamase; to date the genomically encoded bla\(_{OXA-61}\) and the closely related cj0299 are the only described β-lactamase genes of Campylobacter. Cj0299 of C. jejuni NCTC11168 was assigned a novel oxacillinase number OXA-193. Previously, a novel β-lactamase (CjBla2)was identified in two bla\(_{OXA-193}\) negative isolates,P843 and P854. Southern blotting with a probe for bla\(_{OXA-193}\) confirmed that Bla2 is not the product of a mutated bla\(_{OXA-193}\) gene. A further thirteen veterinary isolates of Campylobacter have been identified that have the same phenotype as P843 and P854. Whole genome sequencing of P854 revealed four putative beta-lactamase genes, one of which, P854_1490, encodes a completely novel oxacillinase (OXA-184). PCR screening and sequencing of the other putative CjBla2 producers revealed six to contain the novel oxacillinase. A further five encode a variant of this novel OXA in which a point mutation has led to an amino acid coding change from leucine to isoleucine (OXA-185). These isolates represent a selection of flaA types and were isolated from two separate locations at different times, therefore it is unlikely that they are a clonal population. Two conjugative plasmids, each approximately 45Kb in size, have been identified from two veterinary isolates of Campylobacter. These plasmids have been shown to horizontally transfer resistance to tetracycline and to the β-lactams penicillin, ampicillin and oxacillin, between Campylobacter, a process never previously described. The two β-lactam resistance encoding plasmids thought to contain a β-lactamase gene(s) have been named pBla1 and pBla2. The role of efflux in beta-lactam resistance has also been investigated; inactivation of the efflux pump gene cmeB in the reference strain NCTC11168 resulted in increased susceptibility to a range of beta-lactams including the cephalosporins which Campylobacter are reported to be innately resistant to and have been included in some Campylobacter selective media. The work completed as part of this PhD program has furthered the understanding of beta-lactam resistance in Campylobacter and has demonstrated that it is clearly a multi-faceted mechanism incorporating various chromosomally encoded beta-lactamases, putative transferable beta-lactamases and efflux.

Type of Work:Ph.D. thesis.
Supervisor(s):Piddock, Laura
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Immunity and Infection
Subjects:QR180 Immunology
RC Internal medicine
Institution:University of Birmingham
ID Code:1679
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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