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Antimicrobial Agents and Chemotherapy, December 2004, p. 4829-4834, Vol. 48, No. 12
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.12.4829-4834.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Molecular and Kinetic Comparison of the Novel Extended-Spectrum ß-Lactamases CTX-M-25 and CTX-M-26

Craig J. Munday,1 David A. Boyd,2 Nigel Brenwald,3 Mark Miller,4 Jennifer M. Andrews,3 Richard Wise,3 Michael R. Mulvey,2 and Peter M. Hawkey1*

Antimicrobial Agents Research Group, Division of Immunity and Infection, The Medical School, University of Birmingham,1 Department of Microbiology, City Hospital, Birmingham, United Kingdom,3 Nosocomial Infections, National Microbiology Laboratory, Health Canada, Winnipeg, Manitoba,2 SMBD-Jewish General Hospital, Montreal, Quebec, Canada4

Received 6 January 2004/ Returned for modification 4 April 2004/ Accepted 11 August 2004

CTX-M-25 is a novel extended-spectrum ß-lactamase isolated from a single Canadian Escherichia coli isolate. Susceptibility testing demonstrated that this enzyme confers resistance to both cefotaxime and ceftazidime, but the level of resistance was reduced with the addition of ß-lactamase inhibitors. The blaCTX-M-25 gene was detected on a 111-kb plasmid. It is a member of the CTX-M-8 group and has the closest amino acid identity (99%; three amino acid substitutions) with CTX-M-26. The blaCTX-M-26 gene was detected on a 100-kb plasmid isolated from a Klebsiella pneumoniae strain from the United Kingdom, and plasmid profiling revealed that it showed some homology to the blaCTX-M-25-harboring plasmid. Both CTX-M genes were located downstream of ISEcp1, although the copy upstream of blaCTX-M-25 was disrupted by IS50-A. Comparative kinetic studies of recombinant CTX-M-25 and CTX-M-26 enzymes showed that CTX-M-25 has a higher level of ceftazidime hydrolysis (kcat values, 33 and 0.005 s–1 for CTX-M-25 and CTX-M-26, respectively).


* Corresponding author. Mailing address: Public Health Laboratory, Heartlands Hospital, Bordesley Green East, Birmingham B9 5SS, United Kingdom. Phone: 44 (0) 121 4241240. Fax: 44 (0) 121 772 6229. E-mail: peter.hawkey{at}heartsol.wmids.nhs.uk.


Antimicrobial Agents and Chemotherapy, December 2004, p. 4829-4834, Vol. 48, No. 12
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.12.4829-4834.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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