Cochrane Stephen A, Findlay Brandon, Bakhtiary Alireza, Acedo Jeella Z, Rodriguez-Lopez Eva M, Mercier Pascal, Vederas John C
Department of Chemistry, University of Alberta, Edmonton, AB, Canada T6G 2G2.
National High Field NMR Centre, University of Alberta, Edmonton, AB, Canada T6G 2E1.
Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):11561-11566. doi: 10.1073/pnas.1608623113. Epub 2016 Sep 29.
Tridecaptin A (TriA) is a nonribosomal lipopeptide with selective antimicrobial activity against Gram-negative bacteria. Here we show that TriA exerts its bactericidal effect by binding to the bacterial cell-wall precursor lipid II on the inner membrane, disrupting the proton motive force. Biochemical and biophysical assays show that binding to the Gram-negative variant of lipid II is required for membrane disruption and that only the proton gradient is dispersed. The NMR solution structure of TriA in dodecylphosphocholine micelles with lipid II has been determined, and molecular modeling was used to provide a structural model of the TriA-lipid II complex. These results suggest that TriA kills Gram-negative bacteria by a mechanism of action using a lipid-II-binding motif.
十三肽菌素A（TriA）是一种非核糖体脂肽，对革兰氏阴性菌具有选择性抗菌活性。在此我们表明，TriA通过与内膜上的细菌细胞壁前体脂质II结合发挥其杀菌作用，破坏质子动力势。生化和生物物理分析表明，与脂质II的革兰氏阴性变体结合是膜破坏所必需的，并且只有质子梯度被分散。已确定了在含有脂质II的十二烷基磷酸胆碱胶束中TriA的核磁共振溶液结构，并使用分子建模提供了TriA-脂质II复合物的结构模型。这些结果表明，TriA通过使用脂质II结合基序的作用机制杀死革兰氏阴性菌。
