IMP-4, a Novel Metallo-β-Lactamase from Nosocomial Acinetobacter spp. Collected in Hong Kong between 1994 and 1998
AbstractIMP-4, a Novel Metallo-β-Lactamase from Nosocomial Acinetobacter spp. Collected in Hong Kong between 1994 and 1998 Yiu-Wai Chu 1 , Mariya Afzal-Shah 2 , Elizabeth T. S. Houang 1 , * , Marie-France I. Palepou 2 , Donald J. Lyon 1 , Neil Woodford 2 , and David M. Livermore 2 Department of Microbiology, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China, 1 and Antibiotic Resistance Monitoring and Reference Laboratory, Central Public Health Laboratory, London NW9 5HT, United Kingdom 2 ABSTRACT Between 1994 and 1998, 97 imipenem-resistant Acinetobacter isolates were identified at the Prince of Wales Hospital, Hong Kong, China. A bla IMP PCR product was obtained from 23 of 35 viable cultures; 12 isolates belonged to genomic DNA group 3, 8 belonged to group 2 ( Acinetobacter baumannii ), 2 belonged to group 13TU, and 1 belonged to group 1. The bla IMP homologues were sequenced from two isolates from genomic DNA group 2 and one isolate each from groups 3 and 13TU. The four sequences included an identical 738-bp open reading frame, predicted to encode a polypeptide of 246 amino acids, with 95.6% homology to IMP-1 and 89.3% homology to IMP-2. The new enzyme, designated IMP-4, was partially purified. It had a pI of 8.0 and was strongly active against imipenem and meropenem, with V max values 53 and 8% of that for penicillin G, respectively. Strong activity was also seen against oxyimino-aminothiazolyl cephalosporins but not against aztreonam. Hydrolytic activity was inhibited by EDTA but not by clavulanate or tazobactam. Carbapenem MICs for most bla IMP -positive isolates were 4 to 32 μg/ml, but one isolate with the intact gene was susceptible, with imipenem and meropenem MICs of 0.25 and 0.5 μg/ml, respectively. The latter isolate did not produce the band with a pI of 8.0, and gene expression was inferred to have been lost. None of the isolates studied in detail contained extrachromosomal DNA, and carbapenem resistance was not transmissible to Escherichia coli . Nevertheless, the presence of bla IMP-4 in different genomic DNA groups implies horizontal transfer, and sequences resembling a GTTRRRY integrase-dependent recombination motif were identified in the flanking regions of bla IMP-4 .