Calcium-dependent phospholipid membrane

The phospholipid membrane in the presence of calcium ions (Ca²⁺) serves as a critical structural and functional target for specific classes of antibiotics, most notably the cyclic lipopeptide daptomycin (Humphries et al., 2013, Clinical Infectious Diseases). In this context, calcium ions act as a necessary cofactor that bridges the interaction between the drug and negatively charged (anionic) phospholipids, such as phosphatidylglycerol, which are prevalent in bacterial cell membranes (Muller et al., 2016, Biochimica et Biophysica Acta). Upon binding, the drug-calcium-lipid complex undergoes a conformational change that allows the drug to insert into the bilayer, leading to membrane depolarization, leakage of intracellular ions like potassium, and rapid cell death (Silverman et al., 2003, Antimicrobial Agents and Chemotherapy). This target is primarily exploited to treat serious infections caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). While highly effective against bacteria, the interaction must be selective to avoid damaging host cell membranes, and clinical use requires monitoring for side effects like muscle toxicity and elevated creatine phosphokinase levels (Heidary et al., 2018, Journal of Global Antimicrobial Resistance).

Other names

Anionic phospholipid membraneCalcium-complexed phospholipid bilayerBacterial phospholipid membranePhosphatidylglycerol-rich membrane

Calcium ions (Ca²⁺) facilitate the binding of cyclic lipopeptide antibiotics to anionic phospholipids (specifically phosphatidylglycerol), inducing a conformational change that allows membrane insertion, oligomerization, and subsequent membrane depolarization (Pogliano et al., 2012, Journal of Bacteriology).