Microbial cell wall and cytoplasmic membrane anionic components

Microbial cell wall and cytoplasmic membrane anionic components, such as phosphatidylglycerol (PG), cardiolipin, and teichoic acids, are essential for maintaining the structural integrity and electrochemical gradient of bacterial cells (Epand et al., 2016, Biochimica et Biophysica Acta). These negatively charged molecules serve as the primary docking sites for several classes of antibiotics, including lipopeptides and polymyxins (Heidary et al., 2022, Frontiers in Microbiology). For instance, daptomycin requires calcium ions to form complexes that specifically target PG in Gram-positive membranes, leading to rapid depolarization and potassium efflux (Taylor & Palmer, 2016, Antibiotics). In Gram-negative bacteria, the anionic lipid A component of lipopolysaccharide (LPS) is the target for polymyxins, which disrupt the outer membrane through a displacement of divalent cations (Trimble et al., 2016, Cold Spring Harbor Perspectives in Medicine). These interactions are crucial for the bactericidal activity of these drugs against multi-drug resistant pathogens like MRSA and carbapenem-resistant Enterobacteriaceae. Resistance often arises through the modification of these anionic components, such as the addition of L-lysine to PG by the MprF enzyme, which reduces the net negative charge and repels cationic drugs (Ernst & Peschel, 2011, Nature Reviews Microbiology).

Other names

Bacterial anionic lipidsAnionic cell surface componentsPhosphatidylglycerolCardiolipinTeichoic acidsLipopolysaccharide

Binding to anionic components via electrostatic interactions, often calcium-dependent, leading to membrane depolarization, pore formation, and cell death (Heidary et al., 2022, Frontiers in Microbiology; Trimble et al., 2016, Cold Spring Harbor Perspectives in Medicine).