Bacterial and fungal cytoplasmic membrane lipid bilayer

The bacterial and fungal cytoplasmic membrane lipid bilayer is a vital structural and functional barrier that separates the internal cellular environment from the external milieu. In bacteria, this membrane is characterized by a high proportion of anionic phospholipids, such as phosphatidylglycerol, which facilitates the binding of cationic antimicrobial agents [PMID: 23412472]. Fungal membranes are distinguished by the presence of ergosterol, a sterol essential for membrane fluidity and integrity that is absent in mammalian cells [PMID: 12660211]. This target is central to numerous biological processes, including the maintenance of the electrochemical gradient (proton motive force), nutrient transport, and the coordination of cell wall synthesis. Therapeutic agents targeting the lipid bilayer, such as polymyxins, daptomycin, and amphotericin B, are typically rapidly bactericidal or fungicidal by inducing membrane depolarization or physical pore formation. Despite their high efficacy against multi-drug resistant pathogens, these agents often carry significant safety concerns, particularly nephrotoxicity, due to the potential for off-target effects on host cell membranes [PMID: 21346491]. Consequently, the microbial lipid bilayer remains a critical yet challenging target in the development of anti-infective therapies.

Other names

Microbial cytoplasmic membraneBacterial plasma membraneFungal plasma membraneInner membraneProkaryotic lipid bilayer

Drugs targeting the microbial cytoplasmic membrane lipid bilayer primarily act through physical disruption of the membrane structure. For bacteria, lipopeptides like daptomycin insert into the membrane in a calcium-dependent manner, causing rapid depolarization and ion leakage [PMID: 15105114]. Polymyxins interact with the lipid A component of lipopolysaccharides and phospholipids, leading to increased membrane permeability [PMID: 25130034]. In fungi, polyene antibiotics bind to ergosterol within the lipid bilayer, forming transmembrane pores that allow the leakage of essential intracellular components like potassium ions, leading to cell death [PMID: 12660211].