Microbial cell membrane – non-specific surface structures

The microbial cell membrane is a vital phospholipid bilayer that serves as a selective barrier and a site for essential processes such as ATP synthesis and signal transduction (StatPearls, 2023). In bacteria, it is the site of action for several classes of antibiotics, including polymyxins which target the lipopolysaccharides of Gram-negative bacteria, and daptomycin which disrupts the membrane of Gram-positive organisms (PubMed, PMID: 28232460). Fungal membranes are characterized by the presence of ergosterol, a sterol not found in mammalian cells, making it a primary target for polyene antifungals like amphotericin B (NIH, 2022). Disruption of these structures typically leads to the loss of membrane potential and the leakage of intracellular contents, resulting in rapid cell death. While highly effective against resistant pathogens, drugs targeting the membrane often face challenges regarding selectivity, as seen with the nephrotoxicity associated with systemic polymyxin use (UniProt, 2024). Non-specific surface structures of the membrane are also the primary targets for many antiseptics and disinfectants, which cause generalized protein denaturation and lipid dissolution.

Other names

Bacterial cell membraneFungal cell membraneCytoplasmic membraneMicrobial plasma membraneBacterial lipid bilayer

Drugs targeting the microbial cell membrane act through physical disruption of the lipid bilayer or alteration of its electrochemical gradient. Polymyxins act as cationic detergents that bind to lipopolysaccharides (LPS) in Gram-negative bacteria, displacing divalent cations and destabilizing the membrane (PubMed, PMID: 30634313). Daptomycin inserts into the cytoplasmic membrane of Gram-positive bacteria in a calcium-dependent manner, causing rapid depolarization and the leakage of intracellular ions (StatPearls, 2023). Polyene antifungals like Amphotericin B bind to ergosterol in fungal membranes, creating transmembrane pores that lead to the lethal leakage of potassium and other cellular components (NIH, 2022).