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

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

doi:10.3389/fmicb.2020.561317

Eun-Jeong Yoon, Sun Hee Park + Show 5 more

Open Access

https://doi.org/10.3389/fmicb.2020.561317

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Abstract

A novel Klebsiella pneumoniae carbapenemase (KPC) variant, KPC-55, produced by a K. pneumoniae ST307 strain was characterized. K. pneumoniae 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 blaKPC–55 gene in Escherichia coli 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 blaKPC gene had a T794A alteration compared to the blaKPC–2 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.

Highlights

The β-lactam drugs are currently the most used class of antimicrobial agents; among them, carbapenems are the most potent against Gram-positive and Gram-negative bacteria and have the broadest spectrum of activity (Papp-Wallace et al, 2011)
In South Korea, most of the Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales were K. pneumoniae ST11 belonging to CG235 until 2014 and from 2015, the KPC-producing clone was rapidly exchanged to ST307 (Yoon et al, 2018b)
The K. pneumoniae BS407 strain was recovered from a rectal swab of >80-year-old patient admitted for hospitalization at Inje University Busan Paik Hospital, Busan, South Korea

Summary

Introduction

The β-lactam drugs are currently the most used class of antimicrobial agents; among them, carbapenems are the most potent against Gram-positive and Gram-negative bacteria and have the broadest spectrum of activity (Papp-Wallace et al, 2011). Klebsiella pneumoniae carbapenemase (KPC) is one of the most worrisome carbapenem resistance determinants in clinical settings, because it has broad spectrum of substrates including most β-lactams except cephamycins and it appears to be produced by a broad range of bacterial hosts (Yigit et al, 2001; Nordmann et al, 2011). The recent development regarding the inactivation of class A β-lactamases, including KPC, KPC-55 in Klebsiella pneumoniae ST307 is the possibility to use avibactam in combination with ceftazidime (van Duin and Bonomo, 2016). The spectrum of resistance of the K. pneumoniae ST307 clone was broadened to carbapenems by acquiring genes encoding carbapenemases, such as KPC (Villa et al, 2017). In South Korea, most of the KPC-producing Enterobacterales were K. pneumoniae ST11 belonging to CG235 until 2014 and from 2015, the KPC-producing clone was rapidly exchanged to ST307 (Yoon et al, 2018b)

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