SUMMARY Cellular aggregation is an essential step in the formation of biofilms, which promote fungal survival and persistence in hosts. In many of the known yeast cell adhesion proteins, there are amino acid sequences predicted to form amyloid-like β-aggregates. These sequences mediate amyloid formation in vitro. In vivo, these sequences mediate a phase transition from a disordered state to a partially ordered state to create patches of adhesins on the cell surface. These β-aggregated protein patches are called adhesin nanodomains, and their presence greatly increases and strengthens cell-cell interactions in fungal cell aggregation. Nanodomain formation is slow (with molecular response in minutes and the consequences being evident for hours), and strong interactions lead to enhanced biofilm formation. Unique among functional amyloids, fungal adhesin β-aggregation can be triggered by the application of physical shear force, leading to cellular responses to flow-induced stress and the formation of robust biofilms that persist under flow. Bioinformatics analysis suggests that this phenomenon may be widespread. Analysis of fungal abscesses shows the presence of surface amyloids in situ, a finding which supports the idea that phase changes to an amyloid-like state occur in vivo. The amyloid-coated fungi bind the damage-associated molecular pattern receptor serum amyloid P component, and there may be a consequential modulation of innate immune responses to the fungi. Structural data now suggest mechanisms for the force-mediated induction of the phase change. We summarize and discuss evidence that the sequences function as triggers for protein aggregation and subsequent cellular aggregation, both in vitro and in vivo.

发明内容细胞聚集是生物膜形成中必不可少的步骤，生物膜可促进真菌的存活和在宿主中的持久性。在许多已知的酵母细胞粘附蛋白中，有氨基酸序列预计会形成淀粉样β-聚集体。这些序列在体外介导淀粉样蛋白的形成。体内这些序列介导从无序状态到部分有序状态的相变，以在细胞表面上产生粘附素斑块。这些β聚集的蛋白斑称为粘附素纳米域，它们的存在大大增加并增强了真菌细胞聚集中的细胞间相互作用。纳米域的形成很慢（分子反应在数分钟之内，而后果却持续数小时），而强烈的相互作用导致生物膜形成的增强。在功能淀粉样蛋白中独特的是，真菌黏附素β的聚集可通过施加物理剪切力来触发，从而导致细胞对血流诱导的应激作出反应，并形成在血流中持续存在的坚固的生物膜。生物信息学分析表明，这种现象可能很普遍。原位，这一发现支持了在体内发生相变为淀粉样状态的想法。淀粉样蛋白包被的真菌结合了与损伤相关的分子模式受体血清淀粉样蛋白P成分，因此可能会对真菌的先天免疫应答产生相应的调节作用。现在的结构数据表明了力介导的相变诱导的机制。我们总结并讨论了在体外和体内，该序列可作为蛋白质聚集和后续细胞聚集的触发器。