Epidemiology, genetic dynamics, and transmission of the <i>mcr-1</i> gene in China

Colistin is a broad-spectrum antibiotic that kills bacteria through the disruption of the cell membrane, making it effective against various bacterial infections. Since the first global report of <i>mobile colistin-resistant</i> (<i>mcr-1</i>)-positive bacteria, which were discovered and described by Chinese scientists in 2015, monitoring and research on these bacteria have continuously been conducted. In this study, we analyzed 70 <i>mcr-1</i>-positive strains detected by surveillance hospitals across three different provinces of China, as well as 671 strains screened from the NCBI database that contain the <i>mcr-1</i> gene. The epidemiological analysis indicated that the <i>mcr-1</i> gene had circulated undetected in China for over three decades prior to its first report in 2015 and extensive agricultural use of polymyxins likely initiated the emergence of <i>mcr-1</i> and <i>bla</i>_NDM co-harbouring strains in poultry and livestock, with subsequent fecal-environmental transmission leading to human infections. The genetic dynamics and transmission analysis provides the first detailed elucidation of the adaptive evolutionary migration of <i>mcr-1</i>, which enhanced its dissemination across diverse bacterial hosts and facilitated the emergence of super-resistant <i>Enterobacterales</i> strains and IncHI2(A) super-plasmids co-harbouring <i>mcr-1</i> and <i>bla</i>_NDM.粘菌素（Colistin）是一种广谱抗生素，可通过破坏细菌细胞膜杀灭病原菌，对多种细菌性感染均具有治疗效果。2015年中国科学家发现并报道了全球首例移动粘菌素耐药性（mobile colistin-resistant, mcr-1）阳性细菌，自此针对此类细菌的监测与研究便持续开展。本研究分析了中国三省监测医院检出的70株mcr-1阳性菌株，以及从NCBI数据库中筛选得到的671株携带mcr-1基因的菌株。流行病学分析显示，mcr-1基因在2015年首次被报道前，已在我国隐性传播三十余年；农业领域广泛使用多粘菌素类药物，可能催生了畜禽体内同时携带mcr-1与bla_NDM的菌株，随后通过粪便-环境途径传播进而引发人类感染。本研究的遗传动力学与传播分析首次详细阐明了mcr-1的适应性进化迁移过程，该过程推动了mcr-1在不同细菌宿主间的扩散，并促进了同时携带mcr-1与bla_NDM的超级耐药肠杆菌目（Enterobacterales）菌株及IncHI2(A)型超级质粒的出现。