Harder, better, faster, stronger: Colistin resistance mechanisms in Escherichia coli
Axel B. Janssen, Willem van Schaik
Abstract
The antibiotic colistin (polymyxin E) is an amphipathic, non-ribosomally synthesized, cyclic lipopeptide, which is selectively bactericidal for gram-negative aerobic bacilli, as it targets lipopolysaccharide (LPS) molecules in their outer membranes Colistin first acts by replacing Ca 2+ and Mg 2+ cations that stabilize the outer membrane through electrostatic interactions with the anionic phosphate groups of the lipid A moiety of LPS Colistin then inserts itself into the outer membrane, negatively affecting the integrity of this barrier. However, destabilization of the outer membrane by colistin may not be lethal to the bacterial cell Indeed, the bactericidal activity of colistin appears to be primarily mediated by the permeabilization of the inner membrane through interactions between colistin and the LPS molecules that are located in the outer leaflet of the inner membrane after synthesis in the cytoplasm