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Global epidemiology, genetic environment, risk factors and therapeutic prospects of MCR genes : a current and emerging update
Mmatli, Masego; Mbelle, Nontombi Marylucy; Sekyere, John Osei
BACKGROUND : Mobile colistin resistance (mcr) genes modify Lipid A molecules
of the lipopolysaccharide, changing the overall charge of the outer membrane.
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 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 mcr from food
animals to meat, manure, the environment, and wastewater samples has
increased the risk of transmission to humans via foodborne and vectorborne routes. 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 genes and other antibiotic resistance genes. The
cost of acquiring mcr is reduced by compensatory adaptation mechanisms.
MCR proteins are well conserved structurally and via enzymatic action. Thus,
therapeutics found effective against MCR-1 should be tested against the
remaining MCR proteins.
CONCLUSION: The dissemination of mcr 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 Enterobacteriaceae infections whilst reducing the toxic
effects of colistin.