Host and microbial cell membranes

Host and microbial cell membranes are fundamental biological barriers composed of phospholipid bilayers and associated proteins that define the boundaries of both host cells and microbial pathogens (https://www.ncbi.nlm.nih.gov/books/NBK26871/). In pharmacology, these membranes serve as critical targets for various antimicrobial agents, which exploit differences in lipid composition—such as the presence of ergosterol in fungi or highly anionic lipids in bacteria—to achieve selective toxicity (https://pubmed.ncbi.nlm.nih.gov/24835544/). Drugs targeting microbial membranes, such as polymyxins and daptomycin, often act by forming pores, inducing depolarization, or physically disrupting the bilayer, leading to the leakage of essential ions and cell death (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112029/). While highly effective against resistant pathogens, targeting membranes presents significant therapeutic challenges, particularly the risk of off-target effects on host cell membranes, which can manifest as systemic toxicity like nephrotoxicity (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4141147/). This target entry is considered broad as it encompasses distinct structures across multiple domains of life, each with unique biochemical properties and pharmacological profiles. Understanding the structural and chemical nuances of these membranes is essential for developing next-generation therapeutics with improved selectivity and safety profiles.

Other names

Biological membranesLipid bilayersPlasma membranesCytoplasmic membranesCellular envelopes

Disruption of membrane integrity through pore formation, depolarization of the transmembrane potential, sequestration of essential lipids (e.g., ergosterol or lipid II), and physical dissolution of the lipid bilayer.