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Antimicrobial Agents and Chemotherapy, October 2009, p. 4472-4482, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00688-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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 {triangledown}

Neil Woodford,1* Alessandra Carattoli,2 Edi Karisik,1 Anthony Underwood,1 Matthew J. Ellington,1 and David M. Livermore1

Centre for Infections, Health Protection Agency, London, United Kingdom,1 Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanita, Rome, Italy2

Received 20 May 2009/ Returned for modification 7 July 2009/ Accepted 6 August 2009

We determined the complete nucleotide sequences of three plasmids that encode CTX-M extended-spectrum β-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: blaCTX-M-15, blaOXA-1, blaTEM-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: blaCTX-M-15, blaOXA-1, blaTEM-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, blaCTX-M-3 and blaTEM-1. It probably arose by the transposition of Tn3 and ISEcp1-blaCTX-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 blaCTX-M-3 and blaCTX-M-15 genes on pEK204 and pEK499/pEK516 represent separate escape events, and (iii) IncFII plasmids harboring blaCTX-M-15 have played a crucial role in the global spread of CTX-M-15 ESBLs in E. coli.


* Corresponding author. Mailing address: ARMRL, HPA Centre for Infections, 61 Colindale Avenue, London NW9 5EQ, United Kingdom. Phone: 44-20-8327-7255. Fax: 44-20-8327-6264. E-mail: neil.woodford{at}hpa.org.uk

{triangledown} Published ahead of print on 17 August 2009.


Antimicrobial Agents and Chemotherapy, October 2009, p. 4472-4482, Vol. 53, No. 10
0066-4804/09/$08.00+0     doi:10.1128/AAC.00688-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.