Microbial cell membrane anionic phospholipids and phosphate-containing components (Microbial cell membrane)

Microbial cell membranes and their associated anionic components serve as a fundamental structural barrier and a critical target for various antimicrobial therapies. Unlike mammalian cell membranes, which are predominantly composed of neutral zwitterionic phospholipids like phosphatidylcholine, microbial membranes are enriched with negatively charged (anionic) phospholipids such as phosphatidylglycerol and cardiolipin (Epand et al., 2016, PMID: 27133774). In addition to these lipids, Gram-negative bacteria possess lipopolysaccharides (LPS) and Gram-positive bacteria contain teichoic acids, both of which contribute to a high density of phosphate groups and a strong negative surface charge (Yeaman & Yount, 2003, PMID: 12615781). This distinct biochemical profile allows for the selective targeting of microbes by cationic antimicrobial peptides (AMPs) and lipopeptides, which utilize electrostatic attraction to bind the cell surface. Once bound, these agents can insert into the bilayer, causing physical disruption, pore formation, and rapid depolarization of the membrane potential, ultimately leading to cell death (Malanovic & Lohner, 2016, PMID: 27133774). This mechanism is particularly effective against multi-drug resistant pathogens, although therapeutic challenges include maintaining selectivity to avoid toxicity in human cells.

Other names

Bacterial cell membraneAnionic phospholipidsPhosphatidylglycerolCardiolipinLipopolysaccharideTeichoic acidLipid II

Drugs typically interact via electrostatic attraction to the negatively charged membrane surface, followed by hydrophobic insertion into the lipid bilayer, leading to pore formation, membrane depolarization, and leakage of intracellular contents.