Serratia marcescens 中 blaKPC-2 和 blaNDM-1 的宿主内和种间转移及其地方和全球流行病学。

IF 4.9 2区医学 Q1 INFECTIOUS DISEASES

International Journal of Antimicrobial Agents Pub Date : 2024-09-07 DOI:10.1016/j.ijantimicag.2024.107327

Feilong Zhang , Zhihua Li , Xinmeng Liu , Ziyao Li , Zichen Lei , Jiankang Zhao , Yulin Zhang , Yongli Wu , Xinrui Yang , Binghuai Lu

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引用次数: 0

摘要

研究目的本研究旨在调查产碳青霉烯酶沙雷氏菌耐药基因 blaNDM-1 的种间转移和 blaKPC-2 的种内转移，并探讨产碳青霉烯酶沙雷氏菌（CPSM）在区域和全球范围内的流行和进化特征：方法：通过抗菌药物敏感性测试、质粒共轭和固化、发现转座单元（TU）、外膜囊泡（OMV）、qPCR、全基因组测序和生物信息学分析，确定了 blaKPC-2- 或 blaNDM-1 的种间和种内转移。通过 cgSNP 和最大似然系统发生树探讨了 CPSM 菌株的基因组进化：结果：从一名急性胰腺炎患者的血液中分离出了CPSM S50079菌株，它在一个质粒上同时携带blaKPC-2和blaNDM-1，并能产生携带blaKPC-2或blaNDM-1的TU。我们确定了携带 blaNDM-1 的质粒通过质粒固化、blaNDM-1-harboring 质粒共轭和 OMVs 转移，从产生相同携带 blaNDM-1 的 TU 的普罗维登斯菌（Providencia rettgeri）P50213 转移到 S. marcescens S50079K（一种 S50079 变种）。此外，在 S50079 中还发现了由 IS26 介导的 blaKPC-2 从质粒到染色体的种内转移。可能的是，在另一名肺移植患者中，也发现了由 IncX3 质粒携带的 blaNDM-1 通过质粒转移在 S. marcescens 和 Citrobacter freundii 以及 Enterobacter hormaechei 之间进行种间转移。此外，在同一家医院的 349 株非重复性 S. marcescens 菌株中发现了 11 个 CPSM，在这 8 个 CPSM 中发现了碳青霉烯酶从 blaKPC-2 演化为 blaKPC-2 和 blaNDM-1 的克隆传播，时间跨度长达四年。最后，对从 NCBI 数据库中检索到的 835 个非重复性 S. marcescens 基因组中的 236 个全球 CPSM 进行分析后发现，碳青霉烯酶在全球范围内长期传播和进化，并将导致更多的碳青霉烯酶基因趋同：结论：在CPSM中发现了耐药基因blaNDM-1的种间转移和耐药基因blaKPC-2的种内转移。结论：发现了CPSM中耐药基因blaNDM-1的种间转移和耐药基因blaKPC-2的种内转移，揭示了CPSM的本地传播和全球传播，需要进行更紧迫的监测。

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In-host intra- and inter-species transfer of blaKPC-2 and blaNDM-1 in Serratia marcescens and its local and global epidemiology

Objectives

The aim of this study was to investigate interspecies transfer of resistance gene bla_NDM-1 and intraspecies transfer of resistance gene bla_KPC-2 in Serratia marcescens, and explore the epidemical and evolutionary characteristics of carbapenemase-producing S. marcescens (CPSM) regionally and globally.

Methods

Interspecies and intraspecies transfer of bla_KPC-2- or bla_NDM-1 were identified by antimicrobial susceptibility testing, plasmid conjugation and curing, discovery of transposable units (TUs), outer membrane vesicles (OMVs), qPCR, whole-genome sequencing (WGS) and bioinformatic analysis. The genomic evolution of CPSM strains was explored by cgSNP and maximum-likelihood phylogenetic tree.

Results

CPSM S50079 strain, co-carrying bla_KPC-2 and bla_NDM-1 on one plasmid, was isolated from the blood of a patient with acute pancreatitis and could generate TUs carrying either bla_KPC-2 or bla_NDM-1. The interspecies transfer of bla_NDM-1-carrying plasmid from Providencia rettgeri P50213, producing the identical bla_NDM-1-carrying TUs, to S. marcescens S50079K, an S50079 variant via plasmid curing, was identified through bla_NDM-1-harbouring plasmid conjugation and OMVs transfer. Moreover, the intraspecies transfer of bla_KPC-2, mediated by IS26 from plasmid to chromosome in S50079, was also identified. In another patient, who underwent lung transplantation, interspecies transfer of bla_NDM-1 carried by IncX3 plasmid was identified among S. marcescens and Citrobacter freundii as well as Enterobacter hormaechei via plasmid transfer. Furthermore, 11 CPSM from 349 non-repetitive S. marcescens strains were identified in the same hospital, and clonal dissemination, with carbapenemase evolution from bla_KPC-2 to both bla_KPC-2 and bla_NDM-1, was found in the 8 CPSM across 4 years. Finally, the analysis of 236 global CPSM from 835 non-repetitive S. marcescens genomes, retrieved from the NCBI database, revealed long-term spread and evolution worldwide, and would cause the convergence of more carbapenemase genes.

Conclusions

Interspecies transfer of resistance gene bla_NDM-1 and intraspecies transfer of resistance gene bla_KPC-2 in CPSM were identified. Nosocomial and global dissemination of CPSM were revealed and more urgent surveillance was acquired.

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来源期刊

International Journal of Antimicrobial Agents 医学-传染病学

CiteScore

21.60

自引率

0.90%

发文量

176

审稿时长

36 days

期刊介绍： The International Journal of Antimicrobial Agents is a peer-reviewed publication offering comprehensive and current reference information on the physical, pharmacological, in vitro, and clinical properties of individual antimicrobial agents, covering antiviral, antiparasitic, antibacterial, and antifungal agents. The journal not only communicates new trends and developments through authoritative review articles but also addresses the critical issue of antimicrobial resistance, both in hospital and community settings. Published content includes solicited reviews by leading experts and high-quality original research papers in the specified fields.