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强化美罗培南水解活性的ST307菌株中一种新型KPC变体KPC-55

A Novel KPC Variant KPC-55 in ST307 of Reinforced Meropenem-Hydrolyzing Activity.

作者信息

Yoon Eun-Jeong, Choi You Jeong, Park Sun Hee, Shin Jeong Hwan, Park Sung Gyun, Choi Jong Rak, Jeong Seok Hoon

机构信息

Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, South Korea.

Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea.

出版信息

Front Microbiol. 2020 Oct 7;11:561317. doi: 10.3389/fmicb.2020.561317. eCollection 2020.

Abstract

A novel carbapenemase (KPC) variant, KPC-55, produced by a ST307 strain was characterized. strain BS407 was recovered from an active surveillance rectal swab of a patient newly admitted to a general hospital in Busan, South Korea. Carbapenemase production was confirmed by the modified Hodge test, and the MICs of β-lactams were determined by the broth microdilution method. The whole genome was sequenced. Cloning and expression of the gene in and MIC determination were performed. The enzyme KPC-55 was used for kinetic assays against β-lactams and compared with the KPC-2 enzyme. The new allele of the gene had a T794A alteration compared to the gene, resulting in the amino acid substitution Y264N in the middle of the β9-sheet. Compared to the KPC-2-producing strain, the KPC-55-producing strain exhibited a lower level of resistance to most β-lactam drugs tested, however, the KPC-55 enzyme catalyzed aztreonam and meropenem at an increased efficiency compared to the catalytic activity of KPC-2. KPC subtypes could have varied phenotypes due to alterations in amino acid sequences, and such an unexpected resistance phenotype emphasizes the importance of detailed characterizations for the carbapenemase-producing Enterobacterales.

摘要

对一株ST307菌株产生的新型碳青霉烯酶(KPC)变体KPC-55进行了表征。菌株BS407是从韩国釜山一家综合医院新入院患者的主动监测直肠拭子中分离得到的。通过改良 Hodge 试验确认了碳青霉烯酶的产生,并采用肉汤微量稀释法测定了β-内酰胺类药物的最低抑菌浓度(MIC)。对全基因组进行了测序。进行了该基因在大肠杆菌中的克隆、表达及MIC测定。使用KPC-55酶对β-内酰胺类药物进行动力学分析,并与KPC-2酶进行比较。与KPC基因相比,该基因的新等位基因存在T794A改变,导致β9折叠中部的氨基酸替换为Y264N。与产KPC-2菌株相比,产KPC-55菌株对大多数测试的β-内酰胺类药物表现出较低水平的耐药性,然而,与KPC-2的催化活性相比,KPC-55酶催化氨曲南和美罗培南的效率有所提高。KPC亚型可能由于氨基酸序列的改变而具有不同的表型,这种意外的耐药表型强调了对产碳青霉烯酶肠杆菌进行详细表征的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bcbb/7579404/628678dcb74f/fmicb-11-561317-g001.jpg

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