Figure 2. Selected mechanisms of colistin resistance.

The bactericidal activity of colistin relies on disruption of the bacterial cell membrane, initiated by electrostatic interaction between colistin and the lipid A portion of bacterial LPS. Immediate, albeit non-specific, resistance to colistin is mediated through transcriptional up-regulation of drug efflux pumps. Specific resistance to colistin is facilitated by the plasmid-mediated mcr-1 gene, encoding a phosphoethanolamine transferase, which modifies lipid A with a phosphoethanolamine (PEP) group, preventing interaction between colistin and lipid A.