The emergence of <i>Escherichia coli</i> with CTX-M extended-spectrum beta-lactamases in the United Kingdom

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

The emergence of Escherichia coli with CTX-M extended-spectrum beta-lactamases in the United Kingdom

In the past decade, multi-resistant Escherichia coli with CTX-M enzymes have rapidly become the leading producers of extended-spectrum p-Iactamases (ESBLs) worldwide. E. coli with CTX-M-lS p-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 blacrx-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 blaTFM_1> blaoXA.l along blacrx_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 ofCTX-M-lS 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 determin~nts. 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.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Complete nucleotide sequences of plasmids pEK204, pEK499, and pEK516, encoding CTX-M enzymes in three major Escherichia coli lineages from the United Kingdom, all belonging to the international O25:H4-ST131 clone

We determined the complete nucleotide sequences of three plasmids that encode CTX-M extended-spectrum beta-lactamases (ESBLs) in pulsed-field gel electrophoresis-defined United Kingdom variants (strains A, C, and D) of the internationally prevalent Escherichia coli O25:H4-ST131 clone. Plasmid pEK499 (strain A; 117,536 bp) was a fusion of type FII and FIA replicons and harbored the following 10 antibiotic resistance genes conferring resistance to eight antibiotic classes: bla(CTX-M-15), bla(OXA-1), bla(TEM-1,) aac6'-Ib-cr, mph(A), catB4, tet(A), and the integron-borne dfrA7, aadA5, and sulI genes. pEK516 (strain D; 64,471 bp) belonged to incompatibility group IncFII and carried seven antibiotic resistance genes: bla(CTX-M-15), bla(OXA-1), bla(TEM-1), aac6'-Ib-cr, catB4, and tet(A), all as in pEK499. It also carried aac3-IIa, conferring gentamicin resistance, and was highly related to pC15-1a, a plasmid encoding the CTX-M-15 enzyme in Canada. By contrast, pEK204 (strain C; 93,732 bp) belonged to incompatibility group IncI1 and carried only two resistance genes, bla(CTX-M-3) and bla(TEM-1). It probably arose by the transposition of Tn3 and ISEcp1-bla(CTX-M-3) elements into a pCOLIb-P9-like plasmid. We conclude that (i) United Kingdom variants of the successful E. coli ST131 clone have acquired different plasmids encoding CTX-M ESBLs on separate occasions, (ii) the bla(CTX-M-3) and bla(CTX-M-15) genes on pEK204 and pEK499/pEK516 represent separate escape events, and (iii) IncFII plasmids harboring bla(CTX-M-15) have played a crucial role in the global spread of CTX-M-15 ESBLs in E. coli