Aarhus University, Department of Biomedicine, Aarhus, Denmark.
Elife. 2020 Dec 1;9:e59776. doi: 10.7554/eLife.59776.
The infective ability of the opportunistic pathogen , recognized as the most frequent cause of biofilm-associated infections, is associated with biofilm-mediated resistance to host immune response. Phenol-soluble modulins (PSM) comprise the structural scaffold of biofilms through self-assembly into functional amyloids, but the role of individual PSMs during biofilm formation remains poorly understood and the molecular pathways of PSM self-assembly are yet to be identified. Here we demonstrate high degree of cooperation between individual PSMs during functional amyloid formation. PSMα3 initiates the aggregation, forming unstable aggregates capable of seeding other PSMs resulting in stable amyloid structures. Using chemical kinetics we dissect the molecular mechanism of aggregation of individual PSMs showing that PSMα1, PSMα3 and PSMβ1 display secondary nucleation whereas PSMβ2 aggregates through primary nucleation and elongation. Our findings suggest that various PSMs have evolved to ensure fast and efficient biofilm formation through cooperation between individual peptides.
机会性病原体的感染能力，被认为是生物膜相关感染的最常见原因，与生物膜介导的宿主免疫反应抗性有关。酚可溶性调节蛋白（PSM）通过自组装成功能性淀粉样纤维，构成生物膜的结构支架，但在生物膜形成过程中单个 PSM 的作用仍知之甚少，PSM 自组装的分子途径仍有待确定。在这里，我们证明了在功能性淀粉样纤维形成过程中，各个 PSM 之间存在高度的合作。PSMα3 启动聚集，形成不稳定的聚集体，能够为其他 PSM 播种，从而形成稳定的淀粉样纤维结构。我们利用化学动力学解析了单个 PSM 聚集的分子机制，表明 PSMα1、PSMα3 和 PSMβ1 表现出二次成核，而 PSMβ2 通过初级成核和延伸聚集。我们的发现表明，各种 PSM 通过单个肽之间的合作进化，以确保快速有效地形成生物膜。
