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IMP-68, a Novel IMP-Type Metallo-β-Lactamase in Imipenem-Susceptible Klebsiella pneumoniae

机译：IMP-68，IMIPENEM-易感克雷布氏菌肺炎的新型IMP型Metallo-β-内酰胺酶

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We recently detected a novel variant of an IMP-type metallo-β-lactamase gene ( bla subIMP-68/sub) from meropenem-resistant but imipenem-susceptible Klebsiella pneumoniae TA6363 isolated in Tokyo, Japan. bla subIMP-68/sub encodes a Ser262Gly point mutant of IMP-11, and transformation experiments showed that bla subIMP-68/sub 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 bla subIMP-68/sub 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 bla subIMP-68/sub 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 bla subIMP-68/sub 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.
机译：我们最近检测到来自Meropenem的Imp-型金属-β-乳酰胺基因（BLA Imp-68 ）的新型变体，但在日本东京中孤立的伊索尼姆抗性但易粘连的肺炎群岛肺炎。 BLA IMP-68 编码IMP-11的SER262GLY点突变体，转化实验表明，BLA IMP-68 增加了受体菌株中CarbapeNs的MIC，而MIC Infipenem相对于其他CarbapeNems（包括百家酒）的人没有大大增加。动力学实验表明，IMP-68 ImipeNem水解活性低于其他肉豆蔻的水解，表明TA6363的抗微生物敏感性谱来自IMP-68底物特异性。全基因组测序表明，Bla Imp-68 由位于Chant / M质粒PTMTA63632（88,953μlbP）上的1族整合子（88,953〜BP）覆盖，其通过缀合可转移。质粒的存在性Bla Imp-68 是值得注意的，因为它赋予肉豆蔻酸的抗菌性耐药性，除ImipeNem外，在肠杆菌菌，可能在临床环境中使用抗菌剂影响治疗计划。重要性Imp型金属-β-内酰胺酶包含一组“大5”碳结构酶。这里，从梅洛涅姆抗性但亚翅尼 - 易感克雷布氏菌Ta6363中发现了一种新的BLA <亚β68（含IMP-11的SEL262GLY点突变体的IMP-11的SER262GLY点突变体）。根据其他Imp变体的研究，先前鉴定了Ser262Gly的取代，对底物特异性鉴定为底物特异性，包括IMP-6。我们确认IMP-68表现出弱癌症水解活性，而不是其他碳癌蛋白酶的活性，表明TA6363的抗菌易感曲线源自IMP-68底物特异性，这可能影响在临床环境中使用抗菌剂的治疗策略。值得注意的是，通过ImipeNem的MIC作为鲤鱼代代表的MIC不可检测地赋予碳癌烯抗性，这证明了由于缺乏对其存在而在日本蔓延的类似抗微生物敏感性谱。 。

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