AUTHOR=Mmatli Masego , Mbelle Nontombi Marylucy , Osei Sekyere John 

TITLE=Global epidemiology, genetic environment, risk factors and therapeutic prospects of mcr genes: A current and emerging update

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.941358

DOI=10.3389/fcimb.2022.941358

ISSN=2235-2988

ABSTRACT=<sec><title>Background</title><p>Mobile colistin resistance (<italic>mcr</italic>) genes modify Lipid A molecules of the lipopolysaccharide, changing the overall charge of the outer membrane.</p></sec><sec><title>Results and discussion</title><p>Ten <italic>mcr</italic> genes have been described to date within eleven Enterobacteriaceae species, with <italic>Escherichia coli</italic>, <italic>Klebsiella pneumoniae</italic>, and <italic>Salmonella</italic> species being the most predominant. They are present worldwide in 72 countries, with animal specimens currently having the highest incidence, due to the use of colistin in poultry for promoting growth and treating intestinal infections. The wide dissemination of <italic>mcr</italic> from food animals to meat, manure, the environment, and wastewater samples has increased the risk of transmission to humans <italic>via</italic> foodborne and vector-borne routes. The stability and spread of <italic>mcr</italic> genes were mediated by mobile genetic elements such as the IncHI<sub>2</sub> conjugative plasmid, which is associated with multiple <italic>mcr</italic> genes and other antibiotic resistance genes. The cost of acquiring <italic>mcr</italic> is reduced by compensatory adaptation mechanisms. MCR proteins are well conserved structurally and <italic>via</italic> enzymatic action. Thus, therapeutics found effective against MCR-1 should be tested against the remaining MCR proteins.</p></sec><sec><title>Conclusion</title><p>The dissemination of <italic>mcr</italic> genes into the clinical setting, is threatening public health by limiting therapeutics options available. Combination therapies are a promising option for managing and treating colistin-resistant <italic>Enterobacteriaceae</italic> infections whilst reducing the toxic effects of colistin.</p></sec>