DOI: 10.1101/493668Dec 11, 2018Paper

Structural Insights into Curli CsgA Cross-β Fibril Architecture Inspired Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents

BioRxiv : the Preprint Server for Biology
Sergei PerovMeytal Landau

Abstract

Curli amyloid fibrils secreted by Enterobacteriaceae mediate host cell adhesion and contribute to biofilm formation, thereby promoting bacterial resistance to environmental stressors. Here, we present crystal structures of amyloid-forming segments from the major curlin subunit, CsgA, revealing steric zipper fibrils of tightly mated β-sheets, demonstrating a structural link between curli and human pathological amyloids. We propose that these cross-β segments structure the highly robust curli amyloid core. D-enantiomeric peptides, originally developed to interfere with Alzheimer's disease-associated Amyloid-β, inhibited CsgA fibrillation and reduced biofilm formation in Salmonella typhimurium. Moreover, CsgA fibrils cross-seeded fibrillation of Amyloid-β, providing further support for the proposed structural resemblance and potential for cross-species amyloid interactions. In this study, we provide structural insights into curli formation, offer a novel strategy for disrupting amyloid-structured biofilms, and hypothesize on the formation of self-propagating prion-like species originating from a microbial source that could influence neurodegenerative diseases.

Related Concepts

Alzheimer's Disease
Amyloid
Antineoplastic Agents
Cell Adhesion
Enterobacteriaceae
Environment
Nerve Degeneration
Peptides
Salmonella typhimurium
Leucine Zippers

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