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Measuring prion propagation in single bacteria elucidates mechanism of loss

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...

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Autores principales: Jager, Krista, Orozco-Hidalgo, Maria Teresa, Springstein, Benjamin Lennart, Joly-Smith, Euan, Papazotos, Fotini, McDonough, EmilyKate, Fleming, Eleanor, McCallum, Giselle, Hilfinger, Andreas, Hochschild, Ann, Potvin-Trottier, Laurent
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9882039/
https://www.ncbi.nlm.nih.gov/pubmed/36712035
http://dx.doi.org/10.1101/2023.01.11.523042
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author Jager, Krista
Orozco-Hidalgo, Maria Teresa
Springstein, Benjamin Lennart
Joly-Smith, Euan
Papazotos, Fotini
McDonough, EmilyKate
Fleming, Eleanor
McCallum, Giselle
Hilfinger, Andreas
Hochschild, Ann
Potvin-Trottier, Laurent
author_facet Jager, Krista
Orozco-Hidalgo, Maria Teresa
Springstein, Benjamin Lennart
Joly-Smith, Euan
Papazotos, Fotini
McDonough, EmilyKate
Fleming, Eleanor
McCallum, Giselle
Hilfinger, Andreas
Hochschild, Ann
Potvin-Trottier, Laurent
author_sort Jager, Krista
collection PubMed
description 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.
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spelling pubmed-98820392023-01-28 Measuring prion propagation in single bacteria elucidates mechanism of loss Jager, Krista Orozco-Hidalgo, Maria Teresa Springstein, Benjamin Lennart Joly-Smith, Euan Papazotos, Fotini McDonough, EmilyKate Fleming, Eleanor McCallum, Giselle Hilfinger, Andreas Hochschild, Ann Potvin-Trottier, Laurent bioRxiv Article 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. Cold Spring Harbor Laboratory 2023-01-12 /pmc/articles/PMC9882039/ /pubmed/36712035 http://dx.doi.org/10.1101/2023.01.11.523042 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Jager, Krista
Orozco-Hidalgo, Maria Teresa
Springstein, Benjamin Lennart
Joly-Smith, Euan
Papazotos, Fotini
McDonough, EmilyKate
Fleming, Eleanor
McCallum, Giselle
Hilfinger, Andreas
Hochschild, Ann
Potvin-Trottier, Laurent
Measuring prion propagation in single bacteria elucidates mechanism of loss
title Measuring prion propagation in single bacteria elucidates mechanism of loss
title_full Measuring prion propagation in single bacteria elucidates mechanism of loss
title_fullStr Measuring prion propagation in single bacteria elucidates mechanism of loss
title_full_unstemmed Measuring prion propagation in single bacteria elucidates mechanism of loss
title_short Measuring prion propagation in single bacteria elucidates mechanism of loss
title_sort measuring prion propagation in single bacteria elucidates mechanism of loss
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9882039/
https://www.ncbi.nlm.nih.gov/pubmed/36712035
http://dx.doi.org/10.1101/2023.01.11.523042
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