National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892.
National Institute of General Medical Sciences, NIH, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 2023 Feb 21;120(8):e2211689120. doi: 10.1073/pnas.2211689120. Epub 2023 Feb 14.
Diverse organisms secrete amphipathic biomolecules for competitive gains. However, how cells cope with producing these membrane-permeabilizing molecules is unclear. We focused on the PSM family of secreted amphipathic peptides in the pathogen that uses two ABC transporters, PmtCD and AbcA, to export peptides across the bacterial cell membrane. We found that increased peptide hydrophobicity favors PSM secretion through PmtCD over AbcA and that only PmtCD protected cells against amphipathic peptides. We propose a two-system model in which PmtCD and AbcA independently export PSMs from either membrane or cytosolic environments, respectively. Our model provides a rationale for the encoding of multiple transport systems on diverse biosynthetic gene clusters used to produce distinct amphipathic molecules. In addition, our data serve as a guide for selectively blocking PSM secretion to achieve antimicrobial or antivirulence approaches and to disrupt established roles of PSM-mediated virulence.
不同的生物体为了获得竞争优势而分泌两亲性生物分子。然而，细胞如何应对产生这些破坏细胞膜的分子尚不清楚。我们专注于病原体中分泌的两亲性肽的 PSM 家族，该家族利用两个 ABC 转运蛋白 PmtCD 和 AbcA 将肽跨细菌细胞膜输出。我们发现，增加肽的疏水性有利于通过 PmtCD 而不是 AbcA 进行 PSM 分泌，并且只有 PmtCD 能保护细胞免受两亲性肽的侵害。我们提出了一个双系统模型，其中 PmtCD 和 AbcA 分别独立地将 PSM 从膜或细胞质环境中输出。我们的模型为在用于产生不同两亲性分子的多样化生物合成基因簇上编码多个转运系统提供了依据。此外，我们的数据为有选择性地阻断 PSM 分泌以实现抗菌或抗病毒方法以及破坏 PSM 介导的毒力的既定作用提供了指导。
