title: IMP-4, a novel metallo-beta-lactamase from nosocomial Acinetobacter spp. collected in Hong Kong between 1994 and 1998.
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 microg/ml, but one isolate with the intact gene was susceptible, with imipenem and meropenem MICs of 0.25 and 0.5 microg/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).
authors.affiliation: Department of Microbiology, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
authors.forename: Y W
authors.initials: YW
authors.lastname: Chu
authors.forename: M
authors.initials: M
authors.lastname: Afzal-Shah
authors.forename: E T
authors.initials: ET
authors.lastname: Houang
authors.forename: M I
authors.initials: MI
authors.lastname: Palepou
authors.forename: D J
authors.initials: DJ
authors.lastname: Lyon
authors.forename: N
authors.initials: N
authors.lastname: Woodford
authors.forename: D M
authors.initials: DM
authors.lastname: Livermore
mesh_terms: D000150:Acinetobacter / Q000201:enzymology / Q000235:genetics*; D000151:Acinetobacter Infections / Q000382:microbiology; D000595:Amino Acid Sequence; D003428:Cross Infection / Q000382:microbiology*; D004926:Escherichia coli; D006723:Hong Kong; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D014169:Transformation, Bacterial; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism
chemical_list: C425142:beta-lactamase IMP-4; D001618:beta-Lactamases