Mechanistic basis of antimicrobial resistance mediated by the phosphoethanolamine transferase MCR-1.

ABSTRACT: Polymyxins are used to treat infections caused by multidrug-resistant Gram-negative bacteria. They are cationic peptides that target the negatively charged lipid A component of lipopolysaccharides, disrupting the outer membrane and lysing the cell. Polymyxin resistance is conferred by inner-membrane enzymes, such as phosphoethanolamine transferases, which add positively charged phosphoethanolamine to lipid A. Here, we present the structure of MCR-1, a plasmid-encoded phosphoethanolamine transferase, in its liganded form. The phosphatidylethanolamine donor substrate is bound near the active site in the periplasmic domain, and lipid A is bound over 20 Å away, within the transmembrane region. Integrating structural, biochemical, and drug-resistance data with computational analyses, we propose

SUBMITTER: Zinkle AP 

PROVIDER: S-EPMC12658134 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature