Structural Modification of Lipopolysaccharide Conferred by in Gram-Negative ESKAPE Pathogens

was initially reported as the first plasmid-mediated colistin resistance gene in clinical isolates of and in China and has subsequently been identified worldwide in various species of the family encodes a phosphoethanolamine transferase, and its expression has been shown to generate phosphoethanolamine-modified bis-phosphorylated hexa-acylated lipid A in Here, we investigated the effects of on colistin susceptibility and on lipopolysaccharide structures in laboratory and clinical strains of the Gram-negative ESKAPE (, , , , , and species) pathogens, which are often treated clinically by colistin. The effects of on colistin resistance were determined using MIC assays of laboratory and clinical strains of , , , and Lipid A structural changes resulting from MCR-1 were analyzed by mass spectrometry. The introduction of led to colistin resistance in , , and but only moderately reduced susceptibility in Phosphoethanolamine modification of lipid A was observed consistently for all four species. These findings highlight the risk of colistin resistance as a consequence of expression among ESKAPE pathogens, especially in and Furthermore, the observation that lipid A structures were modified despite only modest increases in colistin MICs in some instances suggests more sophisticated surveillance methods may need to be developed to track the dissemination of or plasmid-mediated phosphoethanolamine transferases in general.