Mechanisms of bactericidal action and resistance of polymyxins for Gram-positive bacteria

Abstract

Polymyxins are cationic antimicrobial peptides used as the last-line therapy to treat multidrug-resistant Gram-negative bacterial infections. The bactericidal activity of polymyxins against Gram-negative bacteria relies on the electrostatic interaction between the positively charged polymyxins and the negatively charged lipid A of lipopolysaccharide (LPS). Given that Gram-positive bacteria lack an LPS-containing outer membrane, it is generally acknowledged that polymyxins are less active against Gram-positive bacteria. However, Gram-positive bacteria produce negatively charged teichoic acids, which may act as the target of polymyxins. More and more studies suggest that polymyxins have potential as a treatment for Gram-positive bacterial infection. This mini-review discusses recent advances in the mechanism of the antibacterial activity and resistance of polymyxins in Gram-positive bacteria.Key Points• Teichoic acids play a key role in the action of polymyxins on Gram-positive bacteria.• Polymyxin kills Gram-positive bacteria by disrupting cell surface and oxidative damage.• Modification of teichoic acids and phospholipids contributes to polymyxin resistance in Gram-positive bacteria.• Polymyxins have potential as a treatment for Gram-positive bacterial infection.

Keywords: Gram-positive bacteria; Mode of action; Polymyxin resistance; Polymyxins.