Genomic insights into the evolution and mechanisms of carbapenem-resistant hypervirulent Klebsiella pneumoniae co-harboring bla_KPC and bla_NDM: implications for public health threat mitigation.

IF 4.6 2区医学 Q1 MICROBIOLOGY

Annals of Clinical Microbiology and Antimicrobials Pub Date : 2024-03-29 DOI:10.1186/s12941-024-00686-3

Qian Wang, Yue Liu, Ran Chen, Meng Zhang, Zaifeng Si, Yueling Wang, Yan Jin, Yuanyuan Bai, Zhen Song, Xinglun Lu, Mingju Hao, Yingying Hao

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引用次数: 0

Abstract

Background: Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) co-producing bla_KPC and bla_NDM poses a serious threat to public health. This study aimed to investigate the mechanisms underlying the resistance and virulence of CR-hvKP isolates collected from a Chinese hospital, with a focus on bla_KPC and bla_NDM dual-positive hvKP strains.

Methods: Five CR-hvKP strains were isolated from a teaching hospital in China. Antimicrobial susceptibility and plasmid stability testing, plasmid conjugation, pulsed-field gel electrophoresis, and whole-genome sequencing (WGS) were performed to examine the mechanisms of resistance and virulence. The virulence of CR-hvKP was evaluated through serum-killing assay and Galleria mellonella lethality experiments. Phylogenetic analysis based on 16 highly homologous carbapenem-resistant K. pneumoniae (CRKP) producing KPC-2 isolates from the same hospital was conducted to elucidate the potential evolutionary pathway of CRKP co-producing NDM and KPC.

Results: WGS revealed that five isolates individually carried three unique plasmids: an IncFIB/IncHI1B-type virulence plasmid, IncFII/IncR-type plasmid harboring KPC-2 and IncC-type plasmid harboring NDM-1. The conjugation test results indicated that the transference of KPC-2 harboring IncFII/IncR-type plasmid was unsuccessful on their own, but could be transferred by forming a hybrid plasmid with the IncC plasmid harboring NDM. Further genetic analysis confirmed that the pJNKPN26-KPC plasmid was entirely integrated into the IncC-type plasmid via the copy-in route, which was mediated by TnAs1 and IS26.

Conclusion: KPC-NDM-CR-hvKP likely evolved from a KPC-2-CRKP ancestor and later acquired a highly transferable bla_NDM-1 plasmid. ST11-KL64 CRKP exhibited enhanced plasticity. The identification of KPC-2-NDM-1-CR-hvKP highlights the urgent need for effective preventive strategies against aggravated accumulation of resistance genes.

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耐碳青霉烯类药物的高病毒性肺炎克雷伯氏菌同时携带 blaKPC 和 blaNDM 的进化和机制的基因组学启示：对减轻公共卫生威胁的影响。

背景：耐碳青霉烯类药物的高病毒性肺炎克雷伯菌（CR-hvKP）可同时产生 blaKPC 和 blaNDM，对公共卫生构成严重威胁。本研究旨在调查从中国医院收集的 CR-hvKP 分离菌株的耐药性和毒力机制，重点研究 blaKPC 和 blaNDM 双阳性 hvKP 菌株：方法：从中国一家教学医院分离出5株CR-hvKP菌株。方法：从中国教学医院分离出5株CR-hvKP菌株，通过抗菌药物敏感性和质粒稳定性检测、质粒共轭、脉冲场凝胶电泳和全基因组测序（WGS）研究其耐药性和毒力机制。通过血清杀灭实验和黑线蝇致死实验评估了 CR-hvKP 的毒力。基于来自同一医院的 16 个产 KPC-2 的高度同源耐碳青霉烯肺炎克菌（CRKP）分离株进行了系统发育分析，以阐明 CRKP 共产 NDM 和 KPC 的潜在进化途径：结果：WGS发现5个分离株分别携带3种独特的质粒：IncFIB/IncHI1B型毒力质粒、携带KPC-2的IncFII/IncR型质粒和携带NDM-1的IncC型质粒。共轭试验结果表明，携带 IncFII/IncR 型质粒的 KPC-2 单独转移不成功，但可以通过与携带 NDM 的 IncC 型质粒形成杂交质粒进行转移。进一步的遗传分析证实，pJNKPN26-KPC 质粒完全是通过拷贝入途径整合到 IncC 型质粒中的，而拷贝入途径是由 TnAs1 和 IS26 介导的：结论：KPC-NDM-CR-hvKP 可能是从 KPC-2-CRKP 祖先进化而来，后来获得了高度可转移的 blaNDM-1 质粒。ST11-KL64 CRKP 表现出更强的可塑性。KPC-2-NDM-1-CR-hvKP的鉴定突出表明，迫切需要有效的预防策略来防止抗性基因的加速积累。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Clinical Microbiology and Antimicrobials MICROBIOLOGY-

CiteScore

8.60

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Annals of Clinical Microbiology and Antimicrobials considers good quality, novel and international research of more than regional relevance. Research must include epidemiological and/or clinical information about isolates, and the journal covers the clinical microbiology of bacteria, viruses and fungi, as well as antimicrobial treatment of infectious diseases. Annals of Clinical Microbiology and Antimicrobials is an open access, peer-reviewed journal focusing on information concerning clinical microbiology, infectious diseases and antimicrobials. The management of infectious disease is dependent on correct diagnosis and appropriate antimicrobial treatment, and with this in mind, the journal aims to improve the communication between laboratory and clinical science in the field of clinical microbiology and antimicrobial treatment. Furthermore, the journal has no restrictions on space or access; this ensures that the journal can reach the widest possible audience.