Global Epidemiology and Genetic Environment of mcr genes: A One Health Systematic Review of Current and Emerging Trends

Abstract

Background:  Mobile colistin resistance (mcr) genes modify Lipid A molecules of the lipopolysaccharide, changing the overall charge of the outer membrane. Methods: A systematic review of all studies published between January 2015 to July 2021 was performed. Included articles described mcr genes in the context of their genetic environment, fitness cost, crystal structure, their enzymatic activity and the risk factors associated with the acquisition of mcr. Studies describing the epidemiology of mcr genes and novel therapeutics were included.Results and Discussion: Ten mcr genes have been described to date within eleven Enterobacteriaceae species, with Escherichia coli, Klebsiella pneumoniae, and Salmonella species being the most predominant. They are present worldwide in 72 countries, with human specimens currently having the highest incidence. This is due to the wide dissemination of mcr in livestock animals, meat, manure, the environment, and wastewater samples, increasing the risk of transmission via foodborne, zoonotic, and vector-borne routes to humans. The stability and spread of mcr genes were mediated by mobile genetic elements such as the IncHI2 conjugative plasmid, which is associated with multiple mcr-variants and other antibiotic resistance genes. The cost of acquiring mcr is reduced by compensatory adaptation mechanisms. MCR proteins are well conserved via structurally. Hence, MCR-1 inhibitors and therapeutics should be applicable to all MCR proteins.Conclusion: Mcr genes have spread from animals into the clinical setting, threatening public health. Combination therapies are a promising option for managing and treating colistin-resistant Enterobacteriaceae isolates whilst reducing the toxic effects of colistin.