mSphere (Oct 2019)

IMP-68, a Novel IMP-Type Metallo-β-Lactamase in Imipenem-Susceptible <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>

  • Hiroaki Kubota,
  • Yasunori Suzuki,
  • Rumi Okuno,
  • Yumi Uchitani,
  • Tsukasa Ariyoshi,
  • Nobuyuki Takemura,
  • Fuminori Mihara,
  • Kazuhisa Mezaki,
  • Norio Ohmagari,
  • Mari Matsui,
  • Satowa Suzuki,
  • Tsuyoshi Sekizuka,
  • Makoto Kuroda,
  • Keiko Yokoyama,
  • Kenji Sadamasu

DOI
https://doi.org/10.1128/mSphere.00736-19
Journal volume & issue
Vol. 4, no. 5

Abstract

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ABSTRACT 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.

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