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Antimicrobial Agents and Chemotherapy, January 2009, p. 69-74, Vol. 53, No. 1
0066-4804/09/$08.00+0     doi:10.1128/AAC.00227-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Novel Chimeric β-Lactamase CTX-M-64, a Hybrid of CTX-M-15-Like and CTX-M-14 β-Lactamases, Found in a Shigella sonnei Strain Resistant to Various Oxyimino-Cephalosporins, Including Ceftazidime{triangledown}

Yukiko Nagano,1 Noriyuki Nagano,1,2 Jun-ichi Wachino,1 Keiko Ishikawa,3 and Yoshichika Arakawa1*

Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, Tokyo,1 Medical Microbiology Laboratory, Funabashi Municipal Medical Center, Funabashi, Chiba,2 Clinical Microbiology Laboratory, Urayasu Ichikawa City Hospital, Urayasu, Chiba, Japan3

Received 19 February 2008/ Returned for modification 24 March 2008/ Accepted 18 October 2008

The plasmid-mediated novel β-lactamase CTX-M-64 was first identified in Shigella sonnei strain UIH-1, which exhibited resistance to cefotaxime (MIC, 1,024 µg/ml) and ceftazidime (MIC, 32 µg/ml). The amino acid sequence of CTX-M-64 showed a chimeric structure of a CTX-M-15-like β-lactamase (N- and C-terminal moieties) and a CTX-M-14-like β-lactamase (central portion, amino acids 63 to 226), suggesting that it originated by homologous recombination between the corresponding genes. The introduction of a recombinant plasmid carrying blaCTX-M-64 conferred resistance to cefotaxime in Escherichia coli, and the activities of cefotaxime and ceftazidime were restored in the presence of clavulanic acid. Of note, CTX-M-64 production could also confer consistent resistance to ceftazidime, which differs from the majority of CTX-M-type enzymes, which poorly hydrolyze ceftazidime. These results were consistent with the kinetic parameters determined with the purified CTX-M-64 enzyme. The blaCTX-M-64 gene was flanked upstream by an ISEcp1 sequence and downstream by an orf477 sequence. The sequence of the 45-bp spacer region between the right inverted repeat (IRR) of ISEcp1 and blaCTX-M-64 was exactly identical to that of ISEcp1-blaCTX-M-15-like. Moreover, the presence of a putative IRR of ISEcp1 at the right end of truncated orf477 is indicative of an ISEcp1-mediated transposition event in the blaCTX-M-64 gene. The emergence of CTX-M-64 by probable homologous recombination would suggest the natural potential of an alternative mechanism for the diversification of CTX-M-type β-lactamases.

* Corresponding author. Mailing address: Department of Bacterial Pathogenesis and Infection Control, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashi-Murayama, Tokyo 208-0011, Japan. Phone: 81-42-561-0771, ext. 3500. Fax: 81-42-561-7173. E-mail: yarakawa{at}nih.go.jp

{triangledown} Published ahead of print on 27 October 2008.

Antimicrobial Agents and Chemotherapy, January 2009, p. 69-74, Vol. 53, No. 1
0066-4804/09/$08.00+0     doi:10.1128/AAC.00227-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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