Lipid A phosphoethanolamine transferase (MCR-1)

Lipid A phosphoethanolamine transferase, most notably the plasmid-encoded MCR-1 variant, is an inner-membrane enzyme in Gram-negative bacteria that plays a pivotal role in antibiotic resistance [1, 16]. Its primary biological function is to catalyze the transfer of a phosphoethanolamine (pEtN) moiety from phosphatidylethanolamine to the lipid A component of lipopolysaccharide (LPS) [4, 10]. This modification reduces the net negative charge of the bacterial outer membrane, which significantly decreases the electrostatic affinity of cationic antimicrobial peptides, such as colistin and polymyxin B [15, 16]. Consequently, the presence of this enzyme allows bacteria to survive treatment with these last-resort antibiotics, posing a severe threat to global public health [6, 14]. The enzyme is a major therapeutic target for the development of adjuvants intended to restore the efficacy of polymyxins against multidrug-resistant pathogens [2, 12]. While no clinical inhibitors are currently approved, experimental compounds and metal chelators like EDTA have shown the ability to inhibit its activity in vitro [1, 17]. The rapid spread of the mcr-1 gene via horizontal gene transfer across various bacterial species, including Escherichia coli and Klebsiella pneumoniae, underscores the urgency of targeting this molecule [13, 16].

Other names

MCR-1EptAPmrCPhosphatidylethanolamine transferase Mcr-1Polymyxin resistance protein MCR-1

Inhibition of the enzymatic transfer of phosphoethanolamine to lipid A to restore the negative charge of the bacterial outer membrane and re-sensitize the bacteria to polymyxin antibiotics [2, 12].