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马来西亚首次获得耐碳青霉烯类肺炎克雷伯菌的基因组见解。

First genomic insights into carbapenem-resistant Klebsiella pneumoniae from Malaysia.

机构信息

Deakin Genomics Centre, Deakin University, Geelong, Victoria, Australia; Centre for Integrative Ecology, School of Life and Environmental Sciences, Deakin University, Geelong, Victoria, Australia; Monash University Malaysia Genomics Facility, Tropical Medicine and Biology Multidisciplinary Platform, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia; School of Science, Monash University Malaysia, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia.

Monash University Malaysia Genomics Facility, Tropical Medicine and Biology Multidisciplinary Platform, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia; School of Science, Monash University Malaysia, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia.

出版信息

J Glob Antimicrob Resist. 2020 Mar;20:153-159. doi: 10.1016/j.jgar.2019.07.008. Epub 2019 Jul 17.

DOI:10.1016/j.jgar.2019.07.008
PMID:31325618
Abstract

OBJECTIVES

Despite the increasing reports of carbapenem-resistant Enterobacteriaceae in Malaysia, genomic resources for carbapenem-resistant clinical strains of Klebsiella pneumoniae (K. pneumoniae) remain unavailable. This study aimed to sequence the genomes of multiple carbapenem-resistant K. pneumoniae strains from Malaysia and to identify the genetic basis for their resistance.

METHODS

Illumina whole genome sequencing was performed on eight carbapenem-resistant K. pneumoniae isolated from a Malaysian hospital. Genetic diversity was inferred from the assembled genomes based on in silico multilocus sequence typing (MLST). In addition, plasmid-derived and chromosome-derived contigs were predicted using the machine learning approach. After genome annotation, genes associated with carbapenem resistance were identified based on similarity searched against the ResFinder database.

RESULTS

The eight K. pneumoniae isolates were grouped into six different sequence types, some of which were represented by a single isolate in the MLST database. Genomic potential for carbapenem-resistance was attributed to the presence of plasmid-localised bla (bla/bla) or bla (bla/bla) in these sequenced strains. The majority of these carbapenem resistance genes was flanked by repetitive (transposase or integrase) sequences, suggesting their potential mobility. This study also reported the first blaharbouring plasmid contig to be assembled for K. pneumoniae, and the second for the genus Klebsiella.

CONCLUSION

This study reported the first genomic resources for carbapenem-resistant K. pneumoniae from Malaysia. The high diversity of carbapenem resistance genes and sequence types uncovered from eight isolates from the same hospital is worrying and indicates an urgent need to improve the genomic surveillance of clinical K. pneumoniae in Malaysia.

摘要

目的

尽管马来西亚不断有报道称肠杆菌科耐碳青霉烯类药物,但仍缺乏耐碳青霉烯类肺炎克雷伯菌(K. pneumoniae)临床分离株的基因组资源。本研究旨在对来自马来西亚的多株耐碳青霉烯类肺炎克雷伯菌进行全基因组测序,并确定其耐药的遗传基础。

方法

对马来西亚一家医院分离的 8 株耐碳青霉烯类肺炎克雷伯菌进行 Illumina 全基因组测序。基于计算机多位点序列分型(MLST),根据组装的基因组推断遗传多样性。此外,使用机器学习方法预测质粒衍生和染色体衍生的基因组。在基因组注释后,根据与 ResFinder 数据库的相似性搜索,鉴定与碳青霉烯类耐药相关的基因。

结果

这 8 株肺炎克雷伯菌分离株分为 6 个不同的序列型,其中一些序列型在 MLST 数据库中仅由单个分离株代表。这些测序菌株中存在 blaNDM-5(blaNDM-5/blaKPC-2)或 blaCTX-M-15(blaCTX-M-15/blaDHA-1)的质粒,这归因于其具有碳青霉烯类耐药的潜在基因组。这些碳青霉烯类耐药基因大多数被重复(转座酶或整合酶)序列包围,表明其潜在的可移动性。本研究还报道了首个组装的blaNDM-5 携带质粒的肺炎克雷伯菌和blaCTX-M-15 携带质粒的肺炎克雷伯菌,这也是该属中第二个被报道的blaNDM-5 携带质粒的肺炎克雷伯菌。

结论

本研究报道了来自马来西亚的首个耐碳青霉烯类肺炎克雷伯菌的基因组资源。从同一家医院的 8 个分离株中发现的碳青霉烯类耐药基因和序列型的多样性很高,令人担忧,这表明迫切需要加强马来西亚临床肺炎克雷伯菌的基因组监测。

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