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Investigating the Spreading and Toxicity of Prion-like Proteins Using the Metazoan Model Organism C. elegans
Published on: January 8, 2015
Measuring prion propagation in single bacteria elucidates mechanism of loss
Krista Jager1, Maria Teresa Orozco-Hidalgo1, Benjamin Lennart Springstein2
1Department of Biology, Concordia University, Montréal, Québec, Canada.
Abstract:
Prions are self-propagating protein aggregates formed by specific proteins that can adopt alternative folds. Prions were discovered as the cause of the fatal transmissible spongiform encephalopathies in mammals, but prions can also constitute non-toxic protein-based elements of inheritance in fungi and other species. Prion propagation has recently been shown to occur in bacteria for more than a hundred cell divisions, yet a fraction of cells in these lineages lost the prion through an unknown mechanism. Here, we investigate prion propagation in single bacterial cells as they divide using microfluidics and fluorescence microscopy. We show that the propagation occurs in two distinct modes with distinct stability and inheritance characteristics. We find that the prion is lost through random partitioning of aggregates to one of the two daughter cells at division. Extending our findings to prion domains from two orthologous proteins, we observe similar propagation and loss properties. Our findings also provide support for the suggestion that bacterial prions can form more than one self-propagating state. We implement a stochastic version of the molecular model of prion propagation from yeast and mammals that recapitulates all the observed single-cell properties. This model highlights challenges for prion propagation that are unique to prokaryotes and illustrates the conservation of fundamental characteristics of prion propagation across domains of life.
Insights
Bacterial prions propagate in two distinct modes, with loss occurring via random aggregate partitioning during cell division. This study reveals conserved prion propagation mechanisms across life.
Area of Science:
- Molecular biology
- Microbiology
- Biophysics
Background:
- Prions are self-propagating protein aggregates with implications in disease and inheritance.
- Bacterial prions are known to propagate for many cell divisions but can be lost.
- The mechanism of prion loss in bacteria remains largely unknown.
Conclusions:
- Bacterial prion propagation exhibits unique prokaryotic challenges and conserved fundamental characteristics across life.
- Random partitioning of aggregates is the primary mechanism for prion loss in bacteria.
- The study provides a comprehensive understanding of bacterial prion dynamics and their broader implications.

