Bacterial outer membrane anionic lipids

Bacterial outer membrane anionic lipids are fundamental structural and functional components of the bacterial cell envelope, primarily found in Gram-negative bacteria. These lipids, which include lipopolysaccharides (LPS), phosphatidylglycerol, and cardiolipin, provide a net negative charge to the cell surface, which is crucial for maintaining membrane integrity and acting as a permeability barrier against toxic substances [PubMed: 28253457]. This anionic nature distinguishes bacterial membranes from the predominantly zwitterionic membranes of mammalian cells, providing a basis for selective toxicity [PubMed: 25130356]. Cationic antimicrobial agents, such as polymyxins (colistin and polymyxin B) and various antimicrobial peptides, target these lipids through strong electrostatic interactions [PubMed: 24255062]. These interactions lead to the displacement of stabilizing divalent cations, membrane disruption, and increased permeability, ultimately resulting in bacterial cell lysis [PubMed: 24550381]. While highly effective against multi-drug resistant pathogens, targeting these lipids can be associated with significant safety concerns, such as nephrotoxicity and neurotoxicity, due to off-target effects or high dosage requirements [PubMed: 27048644].

Other names

Bacterial anionic phospholipidsNegatively charged bacterial lipidsOuter membrane phospholipidsLPS-associated lipidsPhosphatidylglycerolCardiolipin

Cationic drugs bind to the anionic headgroups of lipids via electrostatic attraction, displacing divalent cations (Mg2+ and Ca2+) that stabilize the membrane. This leads to lipid reorganization, membrane thinning, pore formation, and eventual physical rupture of the bacterial cell envelope [PubMed: 25130356, PubMed: 28253457].