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Antimicrobial Agents and Chemotherapy, October 2004, p. 3758-3764, Vol. 48, No. 10
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.10.3758-3764.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Complete Nucleotide Sequence of a 92-Kilobase Plasmid Harboring the CTX-M-15 Extended-Spectrum Beta-Lactamase Involved in an Outbreak in Long-Term-Care Facilities in Toronto, Canada

David A. Boyd,1 Shaun Tyler,1 Sara Christianson,1 Allison McGeer,2 Matthew P. Muller,2 Barbara M. Willey,2 Elizabeth Bryce,3 Michael Gardam,4 Patrice Nordmann,5 Michael R. Mulvey,1* and Canadian Nosocomial Infection Surveillance Program, Health Canada{dagger}

Nosocomial Infections, National Microbiology Laboratory, Health Canada, Winnipeg, Manitoba,1 Mount Sinai Hospital,2 University Health Network, Toronto, Ontario,4 The Vancouver General Hospital, Vancouver, British Columbia, Canada,3 Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Paris, France5

Received 6 January 2004/ Returned for modification 21 April 2004/ Accepted 26 June 2004

A major outbreak involving an Escherichia coli strain that was resistant to expanded-spectrum cephalosporins occurred in Toronto and surrounding regions in 2000 to 2002. We report the complete sequence of a plasmid, pC15-1a, that was found associated with the outbreak strain. Plasmid pC15-1a is a circular molecule of 92,353 bp consisting of two distinct regions. The first is a 64-kb region that is essentially homologous to the non-R-determinant region of plasmid R100 except for several point mutations, a few small insertions and deletions, and the absence of Tn10. The second is a 28.4-kb multidrug resistance region (MDR) that has replaced the R-determinant region of the R100 progenitor and consists mostly of transposons or partial transposons and five copies of the insertion element IS26. All drug resistance genes found in pC15-1a, including the beta-lactamase genes blaCTX-M-15, blaOXA-1, and blaTEM-1, the tetracycline resistance gene tetA, and aminoglycoside resistance genes aac(6')-Ib and aac(3)-II, are located in the MDR. The blaCTX-M-15 gene was found downstream of ISEcp1as part of a transposition unit, as determined from the surrounding sequence. Examination of the plasmids from CTX-M-15-harboring strains isolated from hospitals across Canada showed that pC15-1a was found in several strains isolated from a site in western Canada. Comparison of pC15-1a and pCTX15, found in an E. coli strain isolated in India in 1999, revealed that the plasmids had several features in common, including an R100 backbone and several of the resistance genes, including blaCTX-M-15, blaTEM-1, blaOXA-1, tetA, and aac(6')-Ib.

* Corresponding author. Mailing address: Nosocomial Infections, National Microbiology Laboratory, 1015 Arlington St., Winnipeg, Manitoba, Canada R3E 3R2. Phone: (204) 789-2133. Fax: (204) 789-2018. E-mail: michael_mulvey{at}hc-sc.gc.ca.

{dagger} Contributing members of the Canadian Nosocomial Infection Surveillance Program are listed in Acknowledgments.

Antimicrobial Agents and Chemotherapy, October 2004, p. 3758-3764, Vol. 48, No. 10
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.10.3758-3764.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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