2014-2021年华中和华东地区出现的高病毒性和耐碳青霉烯类肺炎克雷伯菌:一项分子、生物学和流行病学研究。

IF 4 2区 生物学 Q2 MICROBIOLOGY
Chunyang Wu, Yu Huang, Peiyao Zhou, Haojin Gao, Bingjie Wang, Huilin Zhao, Jiao Zhang, Liangxing Wang, Ying Zhou, Fangyou Yu
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引用次数: 0

摘要

背景:近年来,全球对高病毒性和耐碳青霉烯类肺炎克雷伯菌的报道越来越多。本研究旨在比较对碳青霉烯类耐药的高病毒性肺炎克雷伯菌(CR-hvKP)和对碳青霉烯类耐药的高病毒性肺炎克雷伯菌(hv-CRKP)的抗生素耐药性和毒力特征,并确定临床环境中的流行菌株:在本研究中,根据全基因组分析(WGS)、多焦点序列分型(MLST)和抗菌药物敏感性检测的结果,确定了 hv-CRKP 或 CR-hvKP。然后,我们通过抗菌药物敏感性测试和一系列毒力实验(包括生物膜形成能力检测方法、对人血清的耐药性测试、嗜苷酸产生测试、中性粒细胞吞噬实验和Galleria mellonella感染模型)比较了CR-hvKP和hv-CRKP的抗生素耐药性和毒力特征。此外,还进行了通路富集分析,以评估 SNPs 对表型的影响:在这项研究中,我们将 17.4% 的高病毒性和耐碳青霉烯类肺炎克菌菌株归类为 CR-hvKP,82.6% 归类为 hv-CRKP。其中,与 hv-CRKP 菌株相比,84.2%(16/19)携带碳青霉烯酶基因的 CR-hvKP 菌株表现出较低的亚胺培南和美罗培南 MIC 值。体外和体内毒力实验证实了 hv-CRKP 和 CR-hvKP 的毒力潜力,结果显示 CR-hvKP 菌株的毒力与 hv-CRKP 菌株相当。值得注意的是,90株hv-CRKP菌株被分为3种不同的ST类型和8种囊型,每种类型都表现出不同程度的抗性和毒力。我们观察到,在主要的 hv-CRKP 克隆中,ST11-KL64 株具有高水平的抗性和毒力,取代了 ST11-KL47,成为目前流行的亚克隆。KEGG富集分析表明,与柠檬酸循环(TCA循环)、糖酵解/糖原生成、谷胱甘肽代谢、双组分调节系统和叶酸代谢相关的通路在表达不同水平胶囊多糖的群体中显著富集:结论:与 CR-hvKP 菌株相比,hv-CRKP 菌株在医院环境中表现出更大的生存优势。值得注意的是,ST11-KL64 hv-CRKP 菌株表现出高水平的耐药性和高致病性,临床上最需要警惕:临床试验编号:不适用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Emergence of hypervirulent and carbapenem-resistant Klebsiella pneumoniae from 2014 - 2021 in Central and Eastern China: a molecular, biological, and epidemiological study.

Background: In recent years, the hypervirulent and carbapenem-resistant Klebsiella pneumoniae has been increasingly reported worldwide. The objective of this study was to compare the antibiotic resistance and virulence profiles of carbapenem-resistant hypervirulent K.pneumoniae (CR-hvKP) and hypervirulent carbapenem-resistant K.pneumoniae (hv-CRKP) and identify the prevailing strain in clinical settings.

Methods: In this study, hv-CRKP or CR-hvKP were identified based on the results of whole-genome analysis (WGS), multilocus sequence typing (MLST) and the antimicrobial susceptibility testing. We then compared antibiotic resistance and virulence profiles between CR-hvKP and hv-CRKP through the antimicrobial susceptibility testing and a series of virulence experiments including biofilm formation ability detection method, the resistance test against human serum, siderophore production test, neutrophil phagocytosis assay and Galleria mellonella infection model. Additionally, pathway enrichment analysis was conducted to assess the effect of SNPs on the phenotype.

Results: In this study, we categorized 17.4% of hypervirulent and carbapenem-resistant K. pneumoniae strains as CR-hvKP and 82.6% as hv-CRKP. Among them, 84.2% (16/19) of CR-hvKP strains harboring carbapenemase genes exhibited lower imipenem and meropenem MIC values compared to hv-CRKP strains. The virulence potential of hv-CRKP and CR-hvKP was confirmed by using virulence experiments in vitro and in vivo, showing that virulence of the CR-hvKP strains was comparable to that of hv-CRKP strains. Notably, the 90 hv-CRKP strains were classified into 3 different ST types and 8 capsule types, each showing varying degrees of resistance and virulence. We observed that subclonal replacement was within the predominant hv-CRKP clone, with the ST11-KL64 strain, characterized by high-level resistance and virulence emerging as the currently prevailing subclone, replacing ST11-KL47. KEGG enrichment analysis showed that pathways associated with the citrate cycle (TCA cycle), glycolysis/gluconeogenesis, glutathione metabolism, two-component regulatory system, and folate metabolism were significantly enriched among the group expressing different levels of capsular polysaccharides.

Conclusions: The hv-CRKP strains exhibited a greater survival advantage in the hospital environment than CR-hvKP strains. Notably, the ST11-KL64 hv-CRKP strain which displayed a high level of resistance and hypervirulence, warrants the most clinical vigilance.

Clinical trial number: Not applicable.

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来源期刊
BMC Microbiology
BMC Microbiology 生物-微生物学
CiteScore
7.20
自引率
0.00%
发文量
280
审稿时长
3 months
期刊介绍: BMC Microbiology is an open access, peer-reviewed journal that considers articles on analytical and functional studies of prokaryotic and eukaryotic microorganisms, viruses and small parasites, as well as host and therapeutic responses to them and their interaction with the environment.
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