Lipid A phosphoethanolamine transferase (MCR) (MCR)

Lipid A phosphoethanolamine transferase is a bacterial enzyme that plays a pivotal role in the development of resistance to polymyxin antibiotics, such as colistin. It functions by catalyzing the transfer of a phosphoethanolamine (PEA) moiety from phosphatidylethanolamine to the lipid A component of the bacterial lipopolysaccharide (LPS) (Liu et al., 2016, The Lancet Infectious Diseases). This chemical modification reduces the net negative charge of the bacterial outer membrane, which significantly impairs the electrostatic binding of cationic antimicrobial peptides (Gao et al., 2016, Nature Communications). The most notable members of this enzyme family are encoded by the mobile colistin resistance (mcr) genes, which are often located on highly transmissible plasmids, facilitating the rapid spread of resistance across diverse bacterial species (Sun et al., 2018, Journal of Antimicrobial Chemotherapy). Because colistin is considered a last-resort antibiotic for multidrug-resistant Gram-negative infections, these enzymes represent a critical threat to global health. Consequently, they are major targets for the development of small-molecule inhibitors and adjuvants intended to restore the efficacy of polymyxins (Anandan et al., 2017, Scientific Reports). Current research focuses on identifying compounds that can disrupt the zinc-dependent active site of the enzyme to overcome resistance (Hinchliffe et al., 2017, Scientific Reports).

Other names

MCR-1EptAPmrCLipid A PEA transferaseMobile colistin resistance protein

The enzyme catalyzes the transfer of a phosphoethanolamine (PEA) group from phosphatidylethanolamine (PE) to the 1 or 4' phosphate groups of lipid A. This modification reduces the net negative charge of the bacterial outer membrane, thereby decreasing the binding affinity of cationic antimicrobial peptides, such as colistin and polymyxin B, which leads to antibiotic resistance.