, an Inducible Gene Encoding an Acquired Phosphoethanolamine Transferase in Escherichia coli, and Its Origin.

The plasmid-located gene, encoding a putative phosphoethanolamine transferase, was identified in a colistin-resistant human fecal strain belonging to a very rare phylogroup, the D-ST69-O15:H6 clone. This MCR-9 protein shares 33% to 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 Analysis of the lipopolysaccharide of the MCR-9-producing isolate revealed a function similar to that of MCR-1 by adding a phosphoethanolamine group to lipid A and subsequently modifying the structure of the lipopolysaccharide. However, a minor impact on susceptibility to polymyxins was noticed once the gene was cloned and produced in an K-12-derived strain. Nevertheless, we showed here that subinhibitory concentrations of colistin induced the expression of the gene, leading to increased MIC levels. This inducible expression was mediated by a two-component regulatory system encoded by the and genes located downstream of Genetic analysis showed that the gene was carried by an IncHI2 plasmid. analysis revealed that the plasmid-encoded MCR-9 shared significant amino acid identity (ca. 80%) with the chromosomally encoded MCR-like proteins from spp. In particular, 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 genes may circulate silently and remain undetected unless induced by colistin.