Biology of Microorganisms, Ruhr University Bochum, Bochum, Germany.
Antimicrob Agents Chemother. 2012 Nov;56(11):5749-57. doi: 10.1128/AAC.01380-12. Epub 2012 Aug 27.
Mersacidin, gallidermin, and nisin are lantibiotics, antimicrobial peptides containing lanthionine. They show potent antibacterial activity. All three interfere with cell wall biosynthesis by binding lipid II, but they display different levels of interaction with the cytoplasmic membrane. On one end of the spectrum, mersacidin interferes with cell wall biosynthesis by binding lipid II without integrating into bacterial membranes. On the other end of the spectrum, nisin readily integrates into membranes, where it forms large pores. It destroys the membrane potential and causes leakage of nutrients and ions. Gallidermin, in an intermediate position, also readily integrates into membranes. However, pore formation occurs only in some bacteria and depends on membrane composition. In this study, we investigated the impact of nisin, gallidermin, and mersacidin on cell wall integrity, membrane pore formation, and membrane depolarization in Bacillus subtilis. The impact of the lantibiotics on the cell envelope was correlated to the proteomic response they elicit in B. subtilis. By drawing on a proteomic response library, including other envelope-targeting antibiotics such as bacitracin, vancomycin, gramicidin S, or valinomycin, YtrE could be identified as the most reliable marker protein for interfering with membrane-bound steps of cell wall biosynthesis. NadE and PspA were identified as markers for antibiotics interacting with the cytoplasmic membrane.
黏菌素、加替沙星和乳链菌肽是含有硫醚键的抗菌肽，它们具有很强的抗菌活性。这三种抗生素都通过与脂质 II 结合来干扰细胞壁生物合成，但它们与细胞质膜的相互作用程度不同。在一个极端，黏菌素通过与脂质 II 结合而不整合到细菌膜中来干扰细胞壁生物合成。在另一个极端，乳链菌肽很容易整合到膜中，在那里它形成大孔。它破坏膜电位并导致营养物质和离子泄漏。加替沙星处于中间位置，也很容易整合到膜中。然而，只有在某些细菌中才会发生孔形成，并且取决于膜的组成。在这项研究中，我们研究了乳链菌肽、加替沙星和黏菌素对枯草芽孢杆菌细胞壁完整性、膜孔形成和膜去极化的影响。这些抗生素对细胞包膜的影响与它们在枯草芽孢杆菌中引起的蛋白质组反应相关。通过利用蛋白质组反应文库，包括其他针对包膜的抗生素，如杆菌肽、万古霉素、短杆菌肽 S 或缬氨霉素，我们可以鉴定出 YtrE 是干扰细胞壁生物合成中与膜结合步骤的最可靠的标记蛋白。NadE 和 PspA 被鉴定为与细胞质膜相互作用的抗生素的标记蛋白。
