The high incidence of bacterial genes that confer resistance to last-resort antibiotics, such as colistin, caused by mobilized colistin resistance (mcr) genes, poses an unprecedented threat to human health. Understanding the spread, evolution, and distribution of such genes among human populations will help in the development of strategies to diminish their occurrence. To tackle this problem, we investigated the distribution and prevalence of potential mcr genes in the human gut microbiome using a set of bioinformatics tools to screen the Unified Human Gastrointestinal Genome (UHGG) collection for the presence, synteny and phylogeny of putative mcr genes, and co-located antibiotic resistance genes. A total of 2079 antibiotic resistance genes (ARGs) were classified as mcr genes in 2046 metagenome assembled genomes (MAGs), distributed across 1596 individuals from 41 countries, of which 215 were identified in plasmidial contigs. The genera that presented the largest number of mcr-like genes were Suterella and Parasuterella. Other potential pathogens carrying mcr genes belonged to the genus Vibrio, Escherichia and Campylobacter. Finally, we identified a total of 22,746 ARGs belonging to 21 different classes in the same 2046 MAGs, suggesting multi-resistance potential in the corresponding bacterial strains, increasing the concern of ARGs impact in the clinical settings. This study uncovers the diversity of mcr-like genes in the human gut microbiome. We demonstrated the cosmopolitan distribution of these genes in individuals worldwide and the co-presence of other antibiotic resistance genes, including Extended-spectrum Beta-Lactamases (ESBL). Also, we described mcr-like genes fused to a PAP2-like domain in S. wadsworthensis. These novel sequences increase our knowledge about the diversity and evolution of mcr-like genes. Future research should focus on activity, genetic mobility and a potential colistin resistance in the corresponding strains to experimentally validate those findings.

中文翻译：

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人类肠道微生物组中假定的动员粘菌素抗性基因


由动员的粘菌素抗性（mcr）基因引起的对最后手段抗生素（例如粘菌素）产生耐药性的细菌基因的高发生率，对人类健康构成了前所未有的威胁。了解此类基因在人群中的传播、进化和分布将有助于制定减少其发生的策略。为了解决这个问题，我们使用一套生物信息学工具调查了人类肠道微生物组中潜在 mcr 基因的分布和流行率，以筛选统一人类胃肠基因组 (UHGG) 集合中推定 mcr 基因的存在、同线性和系统发育，并共同定位的抗生素抗性基因。共有 2079 个抗生素抗性基因 (ARG) 在 2046 个宏基因组组装基因组 (MAG) 中被归类为 mcr 基因，分布在来自 41 个国家的 1596 个个体中，其中 215 个在质粒重叠群中被鉴定。呈现最多 mcr 样基因的属是 Suterella 和 Parasuterella。其他携带 mcr 基因的潜在病原体属于弧菌属、埃希氏菌属和弯曲杆菌属。最后，我们在相同的 2046 个 MAG 中总共鉴定出了属于 21 个不同类别的 22,746 个 ARG，这表明相应的细菌菌株具有多重耐药潜力，增加了对 ARG 在临床环境中影响的关注。这项研究揭示了人类肠道微生物组中 mcr 样基因的多样性。我们证明了这些基因在全世界个体中的世界性分布以及其他抗生素抗性基因的共存，包括超广谱β-内酰胺酶（ESBL）。此外，我们还描述了 S. wadsworthensis 中与 PAP2 样结构域融合的 mcr 样基因。 这些新颖的序列增加了我们对 mcr 样基因的多样性和进化的了解。未来的研究应侧重于相应菌株的活性、遗传流动性和潜在的粘菌素耐药性，以通过实验验证这些发现。