Dataset Information

Biochemical characterization of IMP-30, a metallo-?-lactamase with enhanced activity toward ceftazidime.

ABSTRACT: IMP-type enzymes constitute a clinically important family of metallo-?-lactamases that has grown dramatically in the past decade to its current 45 known members. Here, we report the biochemical characterization of IMP-30 in comparison to IMP-1, from which it deviates by a single E59K mutation. Kinetics, MIC assays, docking, and molecular dynamics simulations support a scenario in which Lys59 interacts with the ceftazidime R1 group, resulting in increased water access and enhanced turnover and MIC of ceftazidime.

SUBMITTER: Pegg KM

PROVIDER: S-EPMC3811441 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Biochemical characterization of IMP-30, a metallo-β-lactamase with enhanced activity toward ceftazidime.

Pegg Kevin M KM Liu Eleanor M EM Lacuran Alecander E AE Oelschlaeger Peter P

Antimicrobial agents and chemotherapy 20130708 10

IMP-type enzymes constitute a clinically important family of metallo-β-lactamases that has grown dramatically in the past decade to its current 45 known members. Here, we report the biochemical characterization of IMP-30 in comparison to IMP-1, from which it deviates by a single E59K mutation. Kinetics, MIC assays, docking, and molecular dynamics simulations support a scenario in which Lys59 interacts with the ceftazidime R1 group, resulting in increased water access and enhanced turnover and MI ...[more]

PMID: 23836186

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Project description:We recently detected a novel variant of an IMP-type metallo-β-lactamase gene (blaIMP-68) from meropenem-resistant but imipenem-susceptible Klebsiella pneumoniae TA6363 isolated in Tokyo, Japan. blaIMP-68 encodes a Ser262Gly point mutant of IMP-11, and transformation experiments showed that blaIMP-68 increased the MIC of carbapenems in recipient strains, whereas the MIC of imipenem was not greatly increased relative to that of other carbapenems, including meropenem. Kinetics experiments showed that IMP-68 imipenem-hydrolyzing activity was lower than that for other carbapenems, suggesting that the antimicrobial susceptibility profile of TA6363 originated from IMP-68 substrate specificity. Whole-genome sequencing showed that blaIMP-68 is harbored by the class 1 integron located on the IncL/M plasmid pTMTA63632 (88,953 bp), which was transferable via conjugation. The presence of plasmid-borne blaIMP-68 is notable, because it conferred antimicrobial resistance to carbapenems, except for imipenem, on Enterobacteriaceae and will likely affect treatment plans using antibacterial agents in clinical settings.IMPORTANCE IMP-type metallo-β-lactamases comprise one group of the "Big 5" carbapenemases. Here, a novel blaIMP-68 gene encoding IMP-68 (harboring a Ser262Gly point mutant of IMP-11) was discovered from meropenem-resistant but imipenem-susceptible Klebsiella pneumoniae TA6363. The Ser262Gly substitution was previously identified as important for substrate specificity according to a study of other IMP variants, including IMP-6. We confirmed that IMP-68 exhibited weaker imipenem-hydrolyzing activity than that for other carbapenems, demonstrating that the antimicrobial susceptibility profile of TA6363 originated from IMP-68 substrate specificity, with this likely to affect treatment strategies using antibacterial agents in clinical settings. Notably, the carbapenem resistance conferred by IMP-68 was undetectable based on the MIC of imipenem as a carbapenem representative, which demonstrates a comparable antimicrobial susceptibility profile to IMP-6-producing Enterobacteriaceae that previously spread in Japan due to lack of awareness of its existence.

Dataset Information

Biochemical characterization of IMP-30, a metallo-?-lactamase with enhanced activity toward ceftazidime.

Publications

Biochemical characterization of IMP-30, a metallo-β-lactamase with enhanced activity toward ceftazidime.

Similar Datasets

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