Structural Insights into Curli CsgA Cross-[beta] Fibril Architecture Inspire Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents

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 curli subunit, CsgA, revealing steric...

Full description

Saved in:
Bibliographic Details
Published in:PLoS pathogens 2019-08, Vol.15 (8)
Main Authors: Perov, Sergei, Lidor, Ofir, Salinas, Nir, Golan, Nimrod, Tayeb- Fligelman, Einav, Deshmukh, Maya, Willbold, Dieter, Landau, Meytal
Format: Article
Language:English
Subjects:
Alzheimer's disease
Crystal structure
Drug resistance
Enterobacteriaceae
Fibrillation
Glycoproteins
Health aspects
Microbial mats
Nervous system diseases
Neurodegenerative diseases
Novels
Peptides
Risk factors
Salmonella
Salmonella typhimurium
Structure
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 curli subunit, CsgA, revealing steric zipper fibrils of tightly mated [beta]-sheets, demonstrating a structural link between curli and human pathological amyloids. D-enantiomeric peptides, originally developed to interfere with Alzheimer's disease-associated amyloid-[beta], inhibited CsgA fibrillation and reduced biofilm formation in Salmonella typhimurium. Moreover, as previously shown, CsgA fibrils cross-seeded fibrillation of amyloid-[beta], providing support for the proposed structural resemblance and potential for cross-species amyloid interactions. The presented findings provide structural insights into amyloidogenic regions important for curli formation, suggest 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.
ISSN:1553-7366
1553-7374
DOI:10.1371/journal.ppat.1007978