Bacterial and fungal cell membrane phospholipids and surface lipids

Bacterial and fungal cell membrane phospholipids and surface lipids are essential structural components that define the boundary and integrity of microbial cells. These molecules, including anionic phospholipids such as phosphatidylglycerol and cardiolipin in bacteria, and ergosterol or specific phospholipids in fungi, create a semi-permeable barrier and serve as a scaffold for vital membrane proteins (Sant et al., 2016; Epand & Epand, 2011). Unlike the cholesterol-rich and zwitterionic membranes of mammalian cells, microbial membranes often feature a high density of negatively charged lipids and unique surface molecules like lipopolysaccharide (LPS) in Gram-negative bacteria or lipoteichoic acid (LTA) in Gram-positive bacteria (Epand & Epand, 2011; Frontiers in Microbiology, 2022). Therapeutic agents such as polymyxins, daptomycin, and polyenes exploit these biochemical distinctions to selectively bind and disrupt the microbial bilayer (NIH, 2025; Sant et al., 2016). This interaction typically leads to rapid membrane permeabilization, the leakage of essential intracellular ions like potassium, and the dissipation of the membrane potential, ultimately resulting in cell death (Nature, 2025; Epand & Epand, 2011). While these targets are highly effective for treating multidrug-resistant infections, the potential for off-target effects on host cell membranes or mitochondrial lipids remains a significant clinical challenge, often manifesting as nephrotoxicity or neurotoxicity (NIH, 2025; Atlas IDP, 2025). Recent discoveries, such as the antibiotic mandimycin, highlight the potential for targeting specific phospholipids to overcome resistance seen with traditional sterol-binding agents (Nature, 2025).

Other names

Microbial membrane lipidsBacterial membrane phospholipidsFungal membrane lipidsAnionic phospholipidsLipopolysaccharide (LPS)Lipoteichoic acid (LTA)ErgosterolMicrobial cell envelope lipids

Drugs targeting these lipids typically act through electrostatic attraction to anionic surfaces, insertion into the lipid bilayer, and subsequent oligomerization to form pores or disrupt membrane curvature, leading to rapid ion efflux and membrane depolarization.