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Title: The emergence of Escherichia coli with CTX-M extended-spectrum beta-lactamases in the United Kingdom
Author: Karisik, Edi
ISNI:       0000 0001 3595 1402
Awarding Body: Open University
Current Institution: Open University
Date of Award: 2007
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In the past decade, multi-resistant Escherichia coli with CTX-M enzymes have rapidly become the leading producers of extended-spectrum β-Iactamases (ESBLs) worldwide. E. coli with CTX-M-15 β-Iactamases are the most common, and are now endemic in many UK hospitals and in the community. Their epidemiology is complex, including five major epidemic clones as defined by pulsed-field gel electrophoresis, as well as many unrelated producers. This study sought to characterise, at a molecular level, E. coli isolates with CTX-M ESBLs and to investigate their nationwide dissemination, so as to identify the basis for the clinical success of thest? organisms. The molecular mechanisms responsible for the multi-drug resistance phrnotype of representative isolates with CTX-M enzymes were explored and compared, as were their phylogenetic and virulence backgrounds. The genetic support and environment of the various blaCTX-M genes were also investigated. The multi-drug resistance of E. coli with CTX-M enzymes was principally encoded by single plasmids, generally self-transferable. Among producers of CTX-M-15 enzyme, and regardless of their host strain's epidemic status, these plasmids were closely-related (IncFII) and encoded most often blaTEM-1, blaOXA-1 along blaCTX-M-15, as well as aac(6')-Ib-cr, aac(3)-IIa and tet(A). The most prevalent UK clone (A) expressed a lower level of CTX-M-15 enzyme than most other producers, probably owing to an IS26 element located downstream of the gene's normal promoter. Its CTX-M-15-encoding plasmid was not self-transferable in-vitro, but carried twelve genes effecting resistance to eight classes of antibiotics, as well as genes for virulence determinents. Most E. coli with CTX-M enzymes, including the major epidemic clones, belonged to the virulence-associated phylogenetic group B2 or D, but did not harbour more virulence determinants than B2 isolates with non-CTX-M ESBLs. Although related, three slightly distinct virulence profiles were apparent for clonal and non-clonal isolates with CTX-M-15 enzymes. In conclusion, CTX-M ESBLs have rapidly spread in the UK among virulent E. coli isolates, aided by horizontal transfer of multi-resistance plasmids, as well as by clonal spread of epidemic producer strains. Their dissemination worryingly undermines the success of antibiotic therapy, especially in community patients, where few oral options remain.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral