Negatively charged microbial and cellular membranes

Negatively charged microbial and cellular membranes serve as a critical physiological barrier and a selective therapeutic target for various antimicrobial and anticancer agents. Unlike healthy mammalian cell membranes, which primarily display zwitterionic phospholipids like phosphatidylcholine on their outer leaflet, the surfaces of bacteria and many cancer cells are enriched with anionic components such as lipopolysaccharides (LPS), lipoteichoic acids, and phosphatidylserine (Zasloff, 2002; Riedl et al., 2011). This net negative charge allows for the selective recruitment of cationic antimicrobial peptides (AMPs) and lipopeptide antibiotics through strong electrostatic interactions. Upon binding, these agents typically disrupt the membrane's structural integrity via pore formation, depolarization, or detergent-like effects, leading to the leakage of intracellular contents and rapid cell death (Humphries et al., 2013). This target is fundamental to the development of membrane-active therapeutics designed to bypass traditional resistance mechanisms associated with intracellular protein targets, though achieving high selectivity is essential to avoid host toxicities such as hemolysis or nephrotoxicity (Melo et al., 2009).

Other names

Anionic membranesBacterial membranesNegatively charged lipid bilayersAnionic phospholipidsMicrobial lipid bilayers

Cationic molecules interact electrostatically with anionic membrane components such as lipopolysaccharides (LPS) in Gram-negative bacteria, lipoteichoic acid in Gram-positive bacteria, or phosphatidylserine in cancer cells, leading to membrane permeabilization, pore formation, depolarization, and eventual cell lysis (Zasloff, 2002; Humphries et al., 2013).