Gram-negative bacterial cytoplasmic membrane phospholipids

The cytoplasmic membrane of Gram-negative bacteria is a phospholipid bilayer that serves as a critical semi-permeable barrier and a scaffold for essential cellular processes, including energy transduction and lipid synthesis. Unlike the outer membrane, which is rich in lipopolysaccharides, the inner membrane is primarily composed of phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin (Epand et al., 2016). These phospholipids maintain the electrochemical gradient, or proton motive force, necessary for ATP production and active transport. Therapeutic agents such as polymyxins and various antimicrobial peptides target these phospholipids by exploiting the electrostatic attraction between cationic drug molecules and anionic lipid headgroups (Li et al., 2019). This interaction leads to membrane thinning, pore formation, and depolarization, resulting in the rapid leakage of essential ions and metabolites. Because of the structural similarities between bacterial and mammalian membranes, drugs targeting this site must be carefully designed to minimize host toxicity, particularly nephrotoxicity and neurotoxicity (Trimble et al., 2016).

Other names

Bacterial inner membrane phospholipidsGram-negative cytoplasmic membrane lipidsBacterial plasma membrane phospholipidsGram-negative bacterial inner membrane

Drugs typically interact with the negatively charged phospholipids (such as phosphatidylglycerol and cardiolipin) via electrostatic attraction, followed by hydrophobic insertion into the bilayer. This process leads to membrane permeabilization, pore formation, and depolarization, which causes the leakage of essential intracellular ions and metabolites, ultimately resulting in bacterial cell death.