[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]
mcr-9, an inducible gene encoding an acquired phosphoethanolamine transferase in Escherichia coli, and its origin
Nicolas Kieffer, Guilhem Royer, Jean-Winoc Decousser, Anne-Sophie Bourrel, Mattia Palmieri, Jose-Manuel Ortiz De La Rosa, Hervé Jacquier, Erick Denamur, Patrice Nordmann,Laurent Poirel
The plasmid-located mcr-9 gene encoding a putative phosphoethanolamine transferase was identified in a colistin-resistant human fecal Escherichia coli belonging to a very rare phylogroup D-ST69-O15:H6 clone. This MCR-9 protein shares 33-65% identity with the other plasmid-encoded MCR-type enzymes identified (MCR-1- to -8) that have been found as sources of acquired resistance to polymyxins in Enterobacteriaceae. Analysis of the lipopolysaccharide of the MCR-9-producing isolate revealed a similar function as MCR-1 by adding a phosphoethanolamine group to the lipid A and subsequently modifying the structure of the lipopolysaccharide. However, a minor impact on susceptibility to polymyxins was noticed once cloned and produced in an E. coli K-12 derived strain. Nevertheless, we showed here that sub-inhibitory concentrations of colistin induced the expression of the mcr-9 gene, leading to increased MIC levels. This inducible expression was mediated by a two-component regulatory system encoded by the qseC and qseB genes located downstream of mcr-9. Genetic analysis showed that the mcr-9 gene was carried by an IncHI2 plasmid. In silico analysis revealed that the plasmid-encoded MCR-9 shared significant amino acid identity (ca. 80%) with the chromosomally-encoded MCR-like proteins from Buttiauxella spp. In particular, Buttiauxella gaviniae was found to harbor a gene encoding MCR-BG, sharing 84% identity with MCR-9. That gene was neither expressed nor inducible in its original host, which was fully susceptible to polymyxins. This work showed that mcr genes may circulate quite silently and remaining undetected unless induced by colistin.
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Keywords: Antibiotics; Drugs Resistance; MCR9; Colistin; E. Coli.