C6830 Interferes with Cell Membrane

Polymyxin B and colistin (polymyxin E) disrupt the cell membrane integrity of Gram-negative bacteria by binding to membrane phospholipids. Eukaryotic cell membranes have phospholipids similar to Gram-negative bacteria, so the polymyxins are most often used clinically as topical antibiotics.

In contrast, the ionophore antibiotics such as monensin and valinomycin tend to be more active against Gram-positive bacteria, which lack the outer cell membranes. Monensin is an ionophore that forms monovalent ion channels in the cell wall of Gram-positive bacteria and allows the free movement of K+ and Na+ ions along their concentration gradients. Valinomycin is a selective K+ ionophore that triggers mitochondrial transition by facilitating the transport of K+ across the mitochondrial membrane. By altering the intracellular cationic environment of the cell, these agents uncouple mitochondrial oxidative metabolism and inhibit cell growth.