IMP-68, a Novel IMP-Type Metallo-β-Lactamase in Imipenem-Susceptible <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>
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...
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American Society for Microbiology
2019
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oai:doaj.org-article:7b63ec9a5fe34e238045334cf4961b0b2021-11-15T15:27:33ZIMP-68, a Novel IMP-Type Metallo-β-Lactamase in Imipenem-Susceptible <named-content content-type="genus-species">Klebsiella pneumoniae</named-content>10.1128/mSphere.00736-192379-5042https://doaj.org/article/7b63ec9a5fe34e238045334cf4961b0b2019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00736-19https://doaj.org/toc/2379-5042ABSTRACT 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.Hiroaki KubotaYasunori SuzukiRumi OkunoYumi UchitaniTsukasa AriyoshiNobuyuki TakemuraFuminori MiharaKazuhisa MezakiNorio OhmagariMari MatsuiSatowa SuzukiTsuyoshi SekizukaMakoto KurodaKeiko YokoyamaKenji SadamasuAmerican Society for MicrobiologyarticleEnterobacteriaceaeKlebsiellaantibiotic resistancecarbapenemsenzyme kineticsgenome analysisMicrobiologyQR1-502ENmSphere, Vol 4, Iss 5 (2019) |
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DOAJ |
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DOAJ |
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EN |
| topic |
Enterobacteriaceae Klebsiella antibiotic resistance carbapenems enzyme kinetics genome analysis Microbiology QR1-502 |
| spellingShingle |
Enterobacteriaceae Klebsiella antibiotic resistance carbapenems enzyme kinetics genome analysis Microbiology QR1-502 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 IMP-68, a Novel IMP-Type Metallo-β-Lactamase in Imipenem-Susceptible <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> |
| description |
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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Hiroaki Kubota |
| title |
IMP-68, a Novel IMP-Type Metallo-β-Lactamase in Imipenem-Susceptible <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> |
| title_short |
IMP-68, a Novel IMP-Type Metallo-β-Lactamase in Imipenem-Susceptible <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> |
| title_full |
IMP-68, a Novel IMP-Type Metallo-β-Lactamase in Imipenem-Susceptible <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> |
| title_fullStr |
IMP-68, a Novel IMP-Type Metallo-β-Lactamase in Imipenem-Susceptible <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> |
| title_full_unstemmed |
IMP-68, a Novel IMP-Type Metallo-β-Lactamase in Imipenem-Susceptible <named-content content-type="genus-species">Klebsiella pneumoniae</named-content> |
| title_sort |
imp-68, a novel imp-type metallo-β-lactamase in imipenem-susceptible <named-content content-type="genus-species">klebsiella pneumoniae</named-content> |
| publisher |
American Society for Microbiology |
| publishDate |
2019 |
| url |
https://doaj.org/article/7b63ec9a5fe34e238045334cf4961b0b |
| work_keys_str_mv |
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