Microbial cell membrane phospholipids and associated membrane proteins

Microbial cell membrane phospholipids and associated membrane proteins constitute the vital boundary of bacteria and fungi, serving as a selective barrier and a hub for essential metabolic processes. Unlike mammalian membranes, bacterial membranes are rich in anionic phospholipids like phosphatidylglycerol and cardiolipin, while fungal membranes contain ergosterol instead of cholesterol. These biochemical differences allow for selective targeting by various antimicrobial agents. For instance, lipopeptides like daptomycin insert into bacterial membranes in a calcium-dependent manner to cause depolarization, while polymyxins target the lipopolysaccharides and phospholipids of Gram-negative outer and inner membranes. In fungi, polyene antibiotics like amphotericin B bind to ergosterol to form lethal pores. Because the integrity of the microbial membrane is fundamental to cell viability and energy production, its disruption is a highly effective strategy for treating severe infections, although it requires careful management of potential toxicities to host tissues.

Other names

Bacterial cytoplasmic membraneFungal plasma membraneMicrobial lipid bilayerProkaryotic cell membrane

Drugs targeting this complex typically act by binding to specific lipid components (e.g., phosphatidylglycerol or ergosterol) or membrane-anchored precursors (e.g., Lipid II), leading to membrane depolarization, pore formation, or physical disruption of the bilayer. This results in the leakage of essential intracellular ions (like potassium) and metabolites, loss of membrane potential, and rapid cell death (bactericidal or fungicidal effect).