Humans as a Source of Colistin Resistance:In Silico Analysis of Public Metagenomes for the mcr-1 Gene in the Gut Microbiome

Objective: Colistin is our last line of defense in the treatment of infections caused by multidrug-resistant gram-negative pathogens. However, resistance against colistin has been observed worldwide. In a recent study, a plasmid-mediated colistin resistance gene (mcr-1) was identified for the first time. The purpose of the present study was to conduct an in silico search for the mcr-1 gene and the plasmid harboring it in a cohort of human gut microbiomes, which have already been deposited in public metagenome databases in different geographies.Materials and Methods: The gut metagenomes of 344 Chinese and 145 European individuals were investigated. Each metagenome sample consisted of sequencing reads obtained from next-generation sequencing. Each DNA read was aligned against the entire mcr-1 and pHNSHP45 plasmid sequences using the BLASTn program. A nucleotide identity threshold of 95% similarity was set, and the reads aligned under that similarity were filtered out.Results: According to our investigation, 6 out of the 344 individuals in the Chinese cohort harbored the mcr-1 gene andclose homologs of pHNSHP45 plasmid in their gut microbiota, whereas no related genetic elements were found in the European cohort.Conclusion: As the human gut microbiome is one of the key reservoirs of the resistome, the presence of the mcr-1 gene in human microbiota is alarming. It can be said that the dissemination of colistin resistance genes will be more prevalent in the clinic. Further investigations, such as the surveillance of dissemination of related genes, in countries where colistin resistance has become a serious problem, like Turkey, should be considered.