Massive analysis of 64’628 bacterial genomes to decipher a water reservoir and origin of mobile colistin resistance (mcr) gene variants: is there another role for this family of enzymes?

Abstract

Since 2015, new worrying colistin resistance mechanism, mediated by mcr-1 gene has been reported worldwide along with eight newly described variants (mcr-2 to mcr-9) but their source(s) and reservoir(s) remain largely unexplored. Here, we conducted a massive bioinformatic analysis of 64628 downloaded bacterial genomes to investigate the reservoir and origin of these mcr variants. We identified a total of 6651 significant positive hits (aa sequence coverage > 90 % and similarity >50%) with the nine MCR variants from these genomes that include 39 bacterial genera and more than 1050 species. Although these variants could be identified in bacteria from human and animal sources, we found plenty MCR variants in unsuspected bacteria from environmental origin, especially from water sources. The ubiquitous presence of mcr variants in bacteria from water likely suggests another role in the biosphere of these enzymes as an unknown defense system against natural antimicrobial peptides and/or bacteriophage predation.