IBC-1, a novel integron-associated class A β-lactamase with extended-spectrum properties produced by an Enterobacter cloacae clinical strain

A transferable p-lactamase produced by a multidrug-resistant clinical isolate of Enterobacter cloacae was studied. The bin gene was carried by a large (>80-kb) transmissible plasmid, Nucleotide sequence analysis of cloned fragments revealed that it was Dart of a gene cassette carried by a class 1 integron along with other resistance genes, including aac(6')-lb. 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-243, 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.