Abstract
BackgroundThe 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.ResultsA 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.ConclusionThis 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.
Highlights
The high incidence of bacterial genes that confer resistance to last-resort antibiotics, such as colistin, caused by mobilized colistin resistance genes, poses an unprecedented threat to human health
Mobilized colistin resistance (MCR) diversity and distribution in the human gut microbiome We identified a total of 2079 protein sequences classified as MCR (13 MCR-1, 1 MCR-1.2, 9 MCR-2, 634 MCR-3, 456 MCR-4, 966 MCR-5) in 2046 genomes (166 from isolates and 1880 from Metagenomic Assembled Genome (MAG)), present in 1596 individuals from 41 different countries (7.2% from the total 21,866 in the study)
Of the 2079 mcr-like genes, 215 (10.34%), were classified by PlasFlow to be located on plasmids, while 1239 MCRs are classified as chromosomally encoded, and 625 genes were in contigs without classification
Summary
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. Many previous studies have addressed the prevalence of AR in clinical environments [3,4,5], and more recently AR prevalence in non-hospitalized populations too [6, 7]. The advances in high-throughput sequencing and bioinformatics provided access to the human resistome through the analysis of metagenomes and metagenomeassembled genomes
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