A gut bacterial amyloid promotes α-synuclein aggregation and motor impairment in mice
Journal article, 2020
Amyloids are a class of protein with unique self-aggregation properties, and their aberrant accumulation can lead to cellular dysfunctions associated with neurodegenerative diseases. While genetic and environmental factors can influence amyloid formation, molecular triggers and/or facilitators are not well defined. Growing evidence suggests that non-identical amyloid proteins may accelerate reciprocal amyloid aggregation in a prion-like fashion. While humans encode ~30 amyloidogenic proteins, the gut microbiome also produces functional amyloids. For example, curli are cell surface amyloid proteins abundantly expressed by certain gut bacteria. In mice overexpressing the human amyloid α-synuclein (αSyn), we reveal that colonization with curli-producing Escherichia coli promotes αSyn pathology in the gut and the brain. Curli expression is required for E. coli to exacerbate αSyn-induced behavioral deficits, including intestinal and motor impairments. Purified curli subunits accelerate αSyn aggregation in biochemical assays, while oral treatment of mice with a gut-restricted amyloid inhibitor prevents curli-mediated acceleration of pathology and behavioral abnormalities. We propose that exposure to microbial amyloids in the gastrointestinal tract can accelerate αSyn aggregation and disease in the gut and the brain.
neuroscience
Curli
mouse
infectious disease
E. coli
microbiome
microbiology
alpha-synuclein
Author
Timothy R. Sampson
California Institute of Technology (Caltech)
Collin Challis
California Institute of Technology (Caltech)
Neha Jain
University of Michigan
Anastasiya Moiseyenko
California Institute of Technology (Caltech)
Mark S. Ladinsky
California Institute of Technology (Caltech)
Gauri G Shastri
California Institute of Technology (Caltech)
Taren Thron
California Institute of Technology (Caltech)
Brittany D. Needham
California Institute of Technology (Caltech)
Istvan Horvath
Chalmers, Biology and Biological Engineering, Chemical Biology
Justine W Debelius
University of California
Stefan Janssen
University of California
Rob Knight
Department of Computer Science and Engineering
University of California
Pernilla Wittung Stafshede
Chalmers, Biology and Biological Engineering, Chemical Biology
Viviana Gradinaru
California Institute of Technology (Caltech)
Matthew Chapman
University of Michigan
Sarkis K Mazmanian
California Institute of Technology (Caltech)
Published in
eLife
2050084x (eISSN)
Vol. 9 art. no e53111Categorizing
Subject Categories (SSIF 2011)
Biochemistry and Molecular Biology
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Microbiology in the medical area
Identifiers
DOI
10.7554/eLife.53111
PubMed
32043464