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
