The Evolution of Functional Amyloids and Their Impact on Host-Microbe Interactions.

Adv Sci (Weinh)

Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, MI, 48109, USA.

Published: September 2025


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Article Abstract

Amyloids are highly ordered β-sheet-rich structures that are well conserved across the domains of life. Amyloids have a unique repetitive structure that enables autocatalytic self-replication. This property is most well-known in the context of neurodegeneration, in which proteins misfold into amyloid and begin an amyloid cascade resulting in the deposition of large amyloid aggregates characteristic of various diseases such as Alzheimer's disease and Parkinson's disease. The amyloid fold, however, can be pathological or functional. The repetitive nature of amyloids positions self-replicating amyloids as a potential key player in the origin of life. This may explain why, despite the pathogenic potential of amyloids, the amyloid fold is readily found. Many amyloids are not pathogenic and instead they contribute positively to the overall fitness of the cell. Bacteria, for example, use functional amyloids to facilitate biofilm formation, dissemination, storage, adhesion to cells or surfaces, and virulence. Interestingly, the high conservation of the amyloid fold and its ability to self-replicate enables bacterial functional amyloids to accelerate amyloid-associated disease in a human host. Here, the structure, conservation, and biology of the bacterial functional amyloids, as well as their impact on human health, are discussed.

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http://dx.doi.org/10.1002/advs.202510109DOI Listing

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