A bacteria-based genetic assay detects prion formation

Prions are infectious, self-propagating protein aggregates that are notorious for causing devastating neurodegenerative diseases in mammals. Recent evidence supports the existence of prions in bacteria. However, the evaluation of candidate bacterial prion-forming proteins has been hampered by the la...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2019-03, Vol.116 (10), p.4605-4610
Main Authors: Fleming, Eleanor, Yuan, Andy H., Heller, Danielle M., Hochschild, Ann
Format: Article
Language:English
Subjects:
Assaying
Bacteria
Biological Sciences
Campylobacter
Campylobacter - genetics
Campylobacter - metabolism
ClpB protein
Deoxyribonucleic acid
DNA
DNA-binding protein
Domains
Escherichia coli - genetics
Escherichia coli - metabolism
Genes, Reporter
Genetic Techniques
Neurodegenerative diseases
Neurological diseases
Prion protein
Prions
Prions - genetics
Prions - metabolism
Proteins
Self propagation
Single-stranded DNA
Single-stranded DNA-binding protein
Transcription, Genetic
Yeast
Yeasts
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Prions are infectious, self-propagating protein aggregates that are notorious for causing devastating neurodegenerative diseases in mammals. Recent evidence supports the existence of prions in bacteria. However, the evaluation of candidate bacterial prion-forming proteins has been hampered by the lack of genetic assays for detecting their conversion to an aggregated prion conformation. Here we describe a bacteria-based genetic assay that distinguishes cells carrying a model yeast prion protein in its nonprion and prion forms. We then use this assay to investigate the prion-forming potential of single-stranded DNA-binding protein (SSB) of Campylobacter hominis. Our findings indicate that SSB possesses a prion-forming domain that can transition between nonprion and prion conformations. Furthermore, we show that bacterial cells can propagate the prion form over 100 generations in a manner that depends on the disaggregase ClpB. The bacteria-based genetic tool we present may facilitate the investigation of prion-like phenomena in all domains of life.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1817711116