Pathogen membrane sterols and phospholipids

Pathogen membrane sterols and phospholipids are fundamental structural components that define the integrity and functionality of microbial cell membranes. In fungi, ergosterol serves as the primary sterol, regulating membrane fluidity and the activity of membrane-bound enzymes, much like cholesterol does in humans [1, 2]. Bacterial membranes, conversely, are characterized by a high proportion of anionic phospholipids such as phosphatidylglycerol and, in Gram-negative bacteria, the presence of lipopolysaccharides containing lipid A [3]. These molecules are essential for maintaining the electrochemical gradient and protecting the cell from environmental stressors. Because of the distinct chemical differences between pathogen lipids and mammalian cholesterol, they are highly effective targets for antimicrobial therapy [4]. Drugs such as polyenes (e.g., amphotericin B) bind specifically to ergosterol to create lethal pores, while lipopeptides (e.g., daptomycin) and polymyxins target bacterial phospholipids to cause membrane depolarization and physical disruption [3, 5]. However, the therapeutic window can be narrow, as some agents exhibit residual affinity for host cell membranes, leading to notable safety concerns like nephrotoxicity and neurotoxicity [1]. References: [1] Gallis, H. A., et al. (1990). Amphotericin B: 30 years of clinical experience. Reviews of Infectious Diseases. [2] Baginski, M., & Czub, J. (2009). Amphotericin B and its new derivatives - mode of action. Current Drug Metabolism. [3] Trimble, M. J., et al. (2016). Polymyxin: Alternative Mechanisms of Action. Frontiers in Microbiology. [4] Taylor, S. D., & Palmer, M. (2016). The mechanism of action of daptomycin. Frontiers in Immunology. [5] Zhang, Y. Y., & Cheng, J. K. (2022). Fungal Sterols and Their Role in Drug Resistance. Journal of Fungi.

Other names

Microbial membrane lipidsFungal ergosterolBacterial phospholipidsCell membrane lipidsErgosterolLipid A

Direct binding to membrane lipids leading to the formation of transmembrane pores, membrane depolarization, or physical disruption of the lipid bilayer, which causes the leakage of essential intracellular ions and metabolites.