Microbial phospholipid bilayer

The microbial phospholipid bilayer is a fundamental structural and functional barrier in bacteria and fungi, essential for maintaining cellular integrity and regulating the transport of ions and nutrients (Epand et al., 2016). Unlike the zwitterionic membranes of mammalian cells, bacterial membranes are typically rich in anionic phospholipids such as phosphatidylglycerol and cardiolipin, which provide a selective target for cationic antimicrobial agents (Malanovic & Lohner, 2016). In fungi, the presence of ergosterol instead of cholesterol further differentiates the microbial membrane from host cells, allowing for targeted disruption by polyene antifungals (NIH, 2023). Therapeutic agents like daptomycin and polymyxins exploit these differences to bind, insert into, and disrupt the membrane, causing rapid depolarization or physical pore formation that leads to cell death (StatPearls, 2023). This target is highly significant in the treatment of multi-drug resistant (MDR) infections because the membrane's physical integrity is essential for viability and is less prone to simple mutational resistance than specific metabolic enzymes. However, the clinical utility of membrane-targeting drugs is often constrained by their narrow therapeutic window and the risk of systemic toxicities, most notably nephrotoxicity and neurotoxicity, due to partial cross-reactivity with host cell membranes (Nation et al., 2014).

Other names

Bacterial cell membraneBacterial cytoplasmic membraneFungal plasma membraneProkaryotic phospholipid bilayerMicrobial plasma membrane

Direct binding to microbial-specific lipids (e.g., phosphatidylglycerol or ergosterol) followed by membrane insertion and oligomerization, leading to pore formation, depolarization of the transmembrane potential, and leakage of essential intracellular contents (Malanovic & Lohner, 2016; StatPearls, 2023).