College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou, 310014, China.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Appl Microbiol Biotechnol. 2020 May;104(9):3771-3780. doi: 10.1007/s00253-020-10525-y. Epub 2020 Mar 10.
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.
多黏菌素是阳离子型抗菌肽，被用作治疗多重耐药革兰氏阴性菌感染的最后一线药物。多黏菌素对革兰氏阴性菌的杀菌活性依赖于带正电荷的多黏菌素与脂多糖（LPS）中带负电荷的脂 A 之间的静电相互作用。鉴于革兰氏阳性菌缺乏含有 LPS 的外膜，人们普遍认为多黏菌素对革兰氏阳性菌的活性较低。然而，革兰氏阳性菌产生带负电荷的磷壁酸，磷壁酸可能是多黏菌素的作用靶点。越来越多的研究表明，多黏菌素具有治疗革兰氏阳性菌感染的潜力。这篇迷你综述讨论了多黏菌素在革兰氏阳性菌中的抗菌活性和耐药性机制的最新进展。关键点：1. 磷壁酸在多黏菌素对革兰氏阳性菌的作用中起关键作用。2. 多黏菌素通过破坏细胞表面和氧化损伤杀死革兰氏阳性菌。3. 磷壁酸和磷脂的修饰有助于革兰氏阳性菌对多黏菌素的耐药性。4. 多黏菌素具有治疗革兰氏阳性菌感染的潜力。
