限制在家畜中使用秋水仙素后,大肠埃希菌 mcr-1 基因和来自动物和人类基因组的质粒的全球变异

Biel Garcias, Mayra Alejandra Flores, Mercedes Fernández, William Monteith, Ben Pascoe, Samuel K. Sheppard, Marga Martín, Martí Cortey, Laila Darwich
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引用次数: 0

摘要

抗菌素耐药性(AMR)是全球健康面临的重大威胁,耐多药(MDR)细菌克隆已成为一个主要问题。多粘菌素类药物,尤其是可乐定,已重新成为治疗 MDR 革兰氏阴性菌感染的最后手段。然而,在牲畜中使用可乐定会传播可移动的可乐定抗性(mcr)基因,特别是 mcr-1,从而影响人类健康。因此,2017 年禁止在牲畜中使用可乐定,这成为研究细菌适应性的一个自然实验。这项工作的目的是分析世界各地限制使用可乐定后 mcr-1 遗传背景的变化。本研究分析了3163个带有mcr-1基因的大肠埃希菌基因组,这些大肠埃希菌来自人类和家畜宿主,主要来自亚洲(n = 2621)和欧洲(n = 359)。基因特性鉴定发现,IncI2(40.4%)、IncX4(26.7%)和耐多药的 IncHI2(18.8%)是最常见的携带 mcr-1 的质粒。各大洲的质粒存在差异,欧洲最常见的是 IncX4(56.6%),而亚洲则以 IncI2(44.8%)为主。与降低适应性成本有关的启动子变体和 ISApl1 显示出一种独特的关联模式,似乎与适应大肠菌素限制有关,这在各大洲之间存在差异。因此,在禁止使用可乐定后,欧洲转向了专门的 mcr-1 质粒(如 IncX4),而亚洲的 ISApl1 则由于不同启动子变体的流行发生了变化而减少。这些分析表明了在限制使用秋水仙素后 mcr-1 适应性的演变,以及在秋水仙素限制后针对特定地区采取抗 AMR 策略的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Global Variation in Escherichia coli mcr-1 Genes and Plasmids from Animal and Human Genomes Following Colistin Usage Restrictions in Livestock
Antimicrobial resistance (AMR) is a significant global health threat, with multidrug-resistant (MDR) bacterial clones becoming a major concern. Polymyxins, especially colistin, have reemerged as last-resort treatments for MDR Gram-negative infections. However, colistin use in livestock has spread mobile colistin resistance (mcr) genes, notably mcr-1, impacting human health. In consequence, its livestock use was banned in 2017, originating a natural experiment to study bacterial adaptation. The aim of this work was to analyse the changes in the mcr-1 genetic background after colistin restriction across the world. This study analyses 3163 Escherichia coli genomes with the mcr-1 gene from human and livestock hosts, mainly from Asia (n = 2621) and Europe (n = 359). Genetic characterisation identifies IncI2 (40.4%), IncX4 (26.7%), and multidrug-resistant IncHI2 (18.8%) as the most common plasmids carrying mcr-1. There were differences in plasmids between continents, with IncX4 (56.6%) being the most common in Europe, while IncI2 (44.8%) was predominant in Asia. Promoter variants related to reduced fitness costs and ISApl1 showed a distinct pattern of association that appears to be associated with adaptation to colistin restriction, which differed between continents. Thus, after the colistin ban, Europe saw a shift to specialised mcr-1 plasmids as IncX4, while ISApl1 decreased in Asia due to changes in the prevalence of the distinct promoter variants. These analyses illustrate the evolution of mcr-1 adaptation following colistin use restrictions and the need for region-specific strategies against AMR following colistin restrictions.
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