Two Decades of Studying Functional Amyloids in Microorganisms

In the past two decades, amyloids, typically associated with human diseases, have been described to play various functional roles in nearly all life forms. The structural and functional diversity of microbial 'functional amyloids' has dramatically increased in recent years, expanding the canonical definition of these assembled molecules. Here, we provide a broad review of the current understanding of microbial functional amyloids and their diverse roles, putting the spotlight on recent discoveries in the field. We discuss their functions as structural scaffolds, surface-tension modulators, adhesion molecules, cell-cycle and gametogenesis regulators, toxins, and mediators of host–pathogen interactions. We outline how noncanonical amyloid morphologies and sophisticated regulatory mechanisms underlie their functional diversity and emphasize their therapeutic and biotechnological implications and applications. This year marks the 20th anniversary of the discovery that amyloids, typically associated with human diseases, can also play beneficial roles essential for normal cellular physiology.Microbial functional amyloids are extremely diverse and are involved in structural scaffolding and biofilm formation, adhesion, surface-tension modulation, regulation of the cell cycle and gametogenesis, toxicity, host–pathogen interactions, and symbiosis.Structural and regulatory polymorphism of microbial functional amyloid systems underlies their functional diversity.A profound understanding of microbial functional amyloid systems could pave the way towards the development of bioinspired materials and anti-infective therapies.The third decade of functional amyloid research begins with open questions regarding the canonical concept of these assemblies.