Anionic phospholipids in bacterial membranes

Anionic phospholipids, primarily phosphatidylglycerol and cardiolipin, are essential components of the bacterial cytoplasmic membrane that provide a net negative charge to the cell surface [1]. Unlike mammalian cell membranes, which are predominantly composed of neutral zwitterionic lipids like phosphatidylcholine, bacterial membranes are rich in these anionic species, making them ideal targets for selective antimicrobial action [2]. These lipids play critical roles in maintaining membrane integrity, anchoring proteins involved in cell wall synthesis, and facilitating cell division [4]. Therapeutic agents such as daptomycin and polymyxins exploit the electrostatic attraction to these lipids to disrupt the bacterial membrane, leading to ion leakage and metabolic collapse [2, 3]. Because these lipids are fundamental to bacterial survival, they represent a robust target for treating multi-drug resistant infections [5]. However, clinical use must balance efficacy with potential toxicities, such as nephrotoxicity or myopathy, which can arise from off-target interactions or high systemic concentrations [2, 3].

Other names

Bacterial anionic phospholipidsNegatively charged bacterial lipidsPhosphatidylglycerolCardiolipinPhosphatidylserine

Drugs typically bind to the negatively charged headgroups of anionic phospholipids via electrostatic interactions, often facilitated by divalent cations like calcium, leading to membrane insertion, pore formation, depolarization, and rapid cell death [1, 2, 3].