Novel polymyxin resistance gene family mcr-12 from environmental Pigmentiphaga litoralis

Abstract The emergence of mobile colistin resistance ( mcr ) genes threatens the efficacy of polymyxins as last-resort antibiotics for treating multidrug-resistant bacterial infections. Here, we identify a novel environmental mcr gene, mcr-12 , discovered in Pigmentiphaga litoralis from Australian sediment, and evaluate its potential role in the intersection between environmental resistance reservoirs and clinically relevant bacteria. Gene mcr-12 was located within a metal-resistance gene cluster on plasmid pPLE30.2, which also carried a predicted novel β-lactamase gene ( bla OXA-1383 ). Removal of pPLE30.2 increased polymyxin susceptibility 32-fold, while reintroduction of mcr-12 restored resistance. Despite its low amino-acid identity to known MCR enzymes, MCR-12 confers polymyxin resistance by phosphoethanolamine transferase modification of lipid A. Expression of mcr-12 in Pseudomonas spp. and Acinetobacter baumannii conferred polymyxin resistance, suggesting that mcr-12 is compatible between environmental strains and clinical pathogens. The discovery of a new mcr gene from an environmental source and from outside Gammaproteobacteria highlights the need for further surveillance efforts within a One Health framework.