Garcias Biel, Flores Mayra Alejandra, Fernández Mercedes, Monteith William, Pascoe Ben, Sheppard Samuel K, Martín Marga, Cortey Martí, Darwich Laila
Department Sanitat i Anatomia Animals, Veterinary Faculty, Universitat Autònoma de Barcelona (UAB), 08193 Cerdanyola del Vallès, Spain.
Department of Biology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Antibiotics (Basel). 2024 Aug 12;13(8):759. doi: 10.3390/antibiotics13080759.
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 () genes, notably , 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 genetic background after colistin restriction across the world. This study analyses 3163 genomes with the gene from human and livestock hosts, mainly from Asia ( = 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 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 IS 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 plasmids as IncX4, while IS decreased in Asia due to changes in the prevalence of the distinct promoter variants. These analyses illustrate the evolution of adaptation following colistin use restrictions and the need for region-specific strategies against AMR following colistin restrictions.
抗菌药物耐药性（AMR）是对全球健康的重大威胁，多重耐药（MDR）细菌克隆成为主要关注点。多粘菌素，尤其是黏菌素，已重新成为治疗MDR革兰氏阴性菌感染的最后手段。然而，黏菌素在牲畜中的使用传播了可移动的黏菌素耐药（mcr）基因，特别是mcr-1，影响人类健康。因此，其在牲畜中的使用于2017年被禁止，从而产生了一项研究细菌适应性的自然实验。这项工作的目的是分析全球黏菌素限制后mcr基因背景的变化。本研究分析了来自人类和牲畜宿主的3163个带有mcr基因的基因组，主要来自亚洲（n = 2621）和欧洲（n = 359）。遗传特征鉴定表明，IncI2（40.4%）、IncX4（26.7%）和多重耐药的IncHI2（18.8%）是携带mcr的最常见质粒。各大洲之间的质粒存在差异，IncX4（56.6%）在欧洲最为常见，而IncI2（44.8%）在亚洲占主导地位。与适应性成本降低相关的启动子变体和插入序列（IS）显示出一种独特的关联模式，似乎与对黏菌素限制的适应性有关，各大洲之间存在差异。因此，在黏菌素禁令之后，欧洲出现了向诸如IncX4等专门化mcr质粒的转变，而由于不同启动子变体流行率的变化，IS在亚洲减少。这些分析说明了黏菌素使用限制后mcr适应性的演变以及黏菌素限制后针对AMR的区域特定策略的必要性。
