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Antimicrobial Agents and Chemotherapy, September 2000, p. 2247-2253, Vol. 44, No. 9
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

IBC-1, a Novel Integron-Associated Class A beta -Lactamase with Extended-Spectrum Properties Produced by an Enterobacter cloacae Clinical Strain

Panagiota Giakkoupi,1 Leonidas S. Tzouvelekis,2 Athanassios Tsakris,3 Veneta Loukova,1,2 Danai Sofianou,4 and Eva Tzelepi1,*

Department of Bacteriology, Hellenic Pasteur Institute,1 and Laboratory of Antimicrobial Agents, Department of Microbiology, Medical School, National University of Athens,2 Athens, Department of Microbiology, Medical School, Aristotle University of Thessaloniki,3 and Department of Microbiology, Hippokration General Hospital,4 Thessaloniki, Greece

Received 6 December 1999/Returned for modification 4 May 2000/Accepted 26 May 2000

A transferable beta -lactamase produced by a multidrug-resistant clinical isolate of Enterobacter cloacae was studied. The bla gene was carried by a large (>80-kb) transmissible plasmid. Nucleotide sequence analysis of cloned fragments revealed that it was part of a gene cassette carried by a class 1 integron along with other resistance genes, including aac(6')-Ib. The encoded beta -lactamase, designated IBC-1, was a novel class A enzyme that hydrolyzed ceftazidime and cefotaxime and was inhibited by tazobactam and, to a lesser extent, by clavulanate. Also, imipenem exhibited potent inhibitory activity against IBC-1. The enzyme consisted of 287 amino acid residues, including Ser-237, cysteines at positions 69 and 237a, and Arg-244, which may be implicated in its interaction with beta -lactams. In amino acid sequence comparisons, IBC-1 displayed the highest similarity with the chromosomal penicillinase of Yersinia enterocolitica, a carbenicillinase from Proteus mirabilis GN79, the species-specific beta -lactamases of Klebsiella oxytoca, and the carbapenemase Sme-1. However, a phylogenetic association with established beta -lactamase clusters could not be conclusively shown.


* Corresponding author. Mailing address: Department of Bacteriology, Hellenic Pasteur Institute, Vas. Sofias 127, Athens 11521, Greece. Phone: 30 1 6462281. Fax: 30 1 6423498. E-mail: tzelepi{at}otenet.gr.


Antimicrobial Agents and Chemotherapy, September 2000, p. 2247-2253, Vol. 44, No. 9
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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