From the Research
The MCR (mobilized colistin resistance) genes are a family of plasmid-mediated genes that confer resistance to colistin, a last-resort antibiotic used to treat multidrug-resistant infections, with ten identified MCR genes (MCR-1 through MCR-10) to date, as reported in a comprehensive review published in 2021 1.
Overview of MCR Genes
The MCR genes encode phosphoethanolamine transferases that modify lipopolysaccharide by adding phosphoethanolamine to lipid A, reducing colistin's ability to bind to bacterial cell membranes.
- MCR-1, first discovered in China in 2015, is the most widely studied and is primarily found in Enterobacteriaceae like E. coli and Klebsiella.
- MCR-2 through MCR-10 were subsequently discovered in various geographical regions and bacterial species.
- MCR-2 shares about 76% amino acid identity with MCR-1 and was first identified in Belgium.
- MCR-3 has been found in Asia and Europe, while MCR-4 was initially detected in pigs in Italy and Spain.
- MCR-5 was discovered in Germany in Salmonella enterica.
- MCR-6 through MCR-10 are more recently identified variants with more limited geographical distribution.
Concerns and Implications
These genes are particularly concerning because they can spread horizontally between bacteria via plasmids, facilitating rapid dissemination of colistin resistance, as highlighted in a study on the emergence and transmission of plasmid-mediated mobile colistin resistance gene mcr-10 in humans and companion animals published in 2022 2. The emergence of MCR genes threatens the effectiveness of colistin as a treatment option for multidrug-resistant infections, highlighting the urgent need for antimicrobial stewardship and development of new antibiotics, as discussed in a review on colistin and its role in the era of antibiotic resistance published in 2020 3.
Detection and Genotyping
A multiplex polymerase chain reaction (Multi-PCR) protocol has been developed to detect and genotype mobile colistin-resistance genes (mcr-1, mcr-3, mcr-8, mcr-10) in Enterobacteria for clinical laboratory purposes, as reported in a study published in 2021 4. This protocol has been validated by testing clinical isolates of Escherichia coli and Klebsiella from human origin, and has shown full concordance with whole-genome sequence data, displaying higher sensitivity and 100% specificity.