碳青霉烯酶基因 blaNDM-5 和 blaOXA-181 共同携带的 IncX3 质粒的出现。

IF 3.7 Q2 INFECTIOUS DISEASES JAC-Antimicrobial Resistance Pub Date : 2024-05-13 eCollection Date: 2024-06-01 DOI:10.1093/jacamr/dlae073
Hui Zuo, Yo Sugawara, Kohei Kondo, Shizuo Kayama, Sayoko Kawakami, Kohei Uechi, Ami Nakano, Koji Yahara, Motoyuki Sugai
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引用次数: 0

摘要

背景:过去二十年来,带有碳青霉烯酶基因的可传播质粒的传播导致全球产碳青霉烯酶肠杆菌的增加,其中 blaNDM 和 blaOXA 是最普遍的碳青霉烯酶基因:目的:描述在2019-20年日本抗菌药物耐药细菌监测中分离到的同时携带blaNDM-5和blaOXA-181(JBEHAAB-19-0176)的大肠埃希菌,并评估携带这两种基因与只携带一种基因相比的功能优势:方法:使用长、短线程测序法测定了该分离株的全基因组序列。结果:WGS 分析表明,blaNDM1 和 blaNDM2 均携带两种基因:WGS分析表明,blaNDM-5和blaOXA-181由同一IncX3质粒pJBEHAAB-19-0176_NDM-OXA携带。该质粒的遗传学特征表明,该质粒是由携带 blaNDM-5 和 blaOXA-181 的两个典型 IncX3 质粒通过共整合和解析形成的,其中涉及 IS3000 和 IS26 序列上的两个重组事件。在有哌拉西林或头孢泊肟存在的条件下培养时,共同携带 blaNDM-5 和 blaOXA-181 的转化子的生长率明显高于仅携带 blaNDM-5 的转化子。此外,在让两个携带 blaNDM-5 的转化株直接竞争的共培养中,额外携带 blaOXA-181 的菌株表现出明显的生长优势:结论:额外携带 blaOXA-181 的细菌在哌拉西林和头孢泊肟的作用下具有选择性优势。这些发现可能解释了目前产生碳青霉烯酶的肠杆菌的流行病学,其中携带 blaNDM-5 和 blaOXA-48 类基因的细菌已在全球范围内独立出现。
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Emergence of an IncX3 plasmid co-harbouring the carbapenemase genes blaNDM-5 and blaOXA-181.

Background: The spread of transmissible plasmids with carbapenemase genes has contributed to a global increase in carbapenemase-producing Enterobacterales over the past two decades, with blaNDM and blaOXA among the most prevalent carbapenemase genes.

Objectives: To characterize an Escherichia coli isolate co-carrying blaNDM-5 and blaOXA-181 (JBEHAAB-19-0176) that was isolated in the Japan Antimicrobial Resistant Bacterial Surveillance in 2019-20, and to evaluate the functional advantage of carrying both genes as opposed to only one.

Methods: The whole-genome sequence of the isolate was determined using long- and short-read sequencing. Growth assay and co-culture experiments were performed for phenotypic characterization in the presence of different β-lactam antibiotics.

Results: WGS analysis showed that blaNDM-5 and blaOXA-181 were carried by the same IncX3 plasmid, pJBEHAAB-19-0176_NDM-OXA. Genetic characterization of the plasmid suggested that the plasmid emerged through the formation of a co-integrate and resolution of two typical IncX3 plasmids harbouring blaNDM-5 and blaOXA-181, which involved two recombination events at the IS3000 and IS26 sequences. When cultured in the presence of piperacillin or cefpodoxime, the growth rate of the transformant co-harbouring blaNDM-5 and blaOXA-181 was significantly higher than the transformant with only blaNDM-5. Furthermore, in co-culture where the two blaNDM-5-harbouring transformants were allowed to compete directly, the strain additionally harbouring blaOXA-181 showed a marked growth advantage.

Conclusions: The additional carriage of blaOXA-181 confers a selective advantage to bacteria in the presence of piperacillin and cefpodoxime. These findings may explain the current epidemiology of carbapenemase-producing Enterobacterales, in which bacteria carrying both blaNDM-5 and blaOXA-48-like genes have emerged independently worldwide.

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