Pathogen Molecular Genetics Section, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, U.S. National Institutes of Health, 50 South Drive, Bethesda, MD 20814, USA.
Department of Prepharm-Med, College of Natural Sciences, Duksung Women's University, 33 Samyang-ro 144-gil, Seoul 01369, South Korea.
Int J Med Microbiol. 2018 Aug;308(6):675-682. doi: 10.1016/j.ijmm.2017.08.010. Epub 2017 Sep 1.
Phenol-soluble modulins (PSMs) are alpha-helical, amphipathic peptides that have multiple functions in staphylococcal physiology and virulence. Recent research has suggested that PSMs form amyloid fibrils and amyloids are involved in PSM-mediated phenotypes such as cytolysis and biofilm stability. While we observed PSM amyloid formation using electron microscopy and dye assays, there were no apparent differences in the production of extracellular fibrous material between a PSM-deficient strain and the isogenic wild-type strain. Furthermore, we detected no correlation between cytolytic or pro-inflammatory activities with the propensity of PSM derivatives to form amyloids. In addition, we propose a model based on our finding of non-specific attachment of PSMs to DNA, which we here report results in resistance to DNase digestion, explaining previous findings on PSM-mediated biofilm stability without the necessity to assume amyloid involvement. Collectively, our results indicate that PSM amyloid formation may not be of major relevance for known key biological functions of PSMs. Intriguingly, however, we found that amyloid-forming capacity of PSMalpha3 allows almost no amino acid exchanges, suggesting importance of amyloid formation in possibly yet unknown functions of PSMs.
酚可溶性调节素（PSMs）是一种具有多种功能的α-螺旋、两亲性肽，在葡萄球菌生理和毒力中起作用。最近的研究表明，PSMs 形成淀粉样纤维，淀粉样蛋白参与 PSM 介导的表型，如细胞溶解和生物膜稳定性。虽然我们使用电子显微镜和染料测定观察到 PSM 淀粉样形成，但在 PSM 缺陷菌株和同源野生型菌株之间，细胞外纤维物质的产生没有明显差异。此外，我们没有检测到细胞溶解或促炎活性与 PSM 衍生物形成淀粉样蛋白的倾向之间存在相关性。此外，我们根据我们发现的 PSM 与 DNA 的非特异性结合提出了一个模型，我们在这里报告的结果表明对 DNA 酶消化的抗性，解释了先前关于 PSM 介导的生物膜稳定性的发现，而无需假设淀粉样蛋白的参与。总的来说，我们的结果表明，PSM 淀粉样形成可能与 PSM 已知关键生物学功能没有主要关系。然而，有趣的是，我们发现 PSMalpha3 的淀粉样形成能力几乎不允许任何氨基酸交换，这表明淀粉样形成在 PSM 可能未知的功能中很重要。
