title: Direct assessment in bacteria of prionoid propagation and phenotype selection by Hsp70 chaperone.
abstract: Protein amyloid aggregates epigenetically determine either advantageous or proteinopathic phenotypes. Prions are infectious amyloidogenic proteins, whereas prionoids lack infectivity but spread from mother to daughter cells. While prion amyloidosis has been studied in yeast and mammalian cells models, the dynamics of transmission of an amyloid proteinopathy has not been addressed yet in bacteria. Using time-lapse microscopy and a microfluidic set-up, we have assessed in Escherichia coli the vertical transmission of the amyloidosis caused by the synthetic bacterial model prionoid RepA-WH1 at single cell resolution within their lineage context. We identify in vivo the coexistence of two strain-like types of amyloid aggregates within a genetically identical population and a controlled homogeneous environment. The amyloids are either toxic globular particles or single comet-shaped aggregates that split during cytokinesis and exhibit milder toxicity. Both segregate and propagate in sublineages, yet show interconversion. ClpB (Hsp104) chaperone, key for spreading of yeast prions, has no effect on the dynamics of the two RepA-WH1 aggregates. However, the propagation of the comet-like species is DnaK (Hsp70)-dependent. The bacterial RepA-WH1 prionoid thus provides key qualitative and quantitative clues on the biology of intracellular amyloid proteinopathies.
authors.affiliation: Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas - CSIC, C/ Ramiro de Maeztu 9, Madrid, E-28040, Spain.
authors.forename: Fátima
authors.initials: F
authors.lastname: Gasset-Rosa
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Coquel
authors.forename: María
authors.initials: M
authors.lastname: Moreno-Del Álamo
authors.forename: Peipei
authors.initials: P
authors.lastname: Chen
authors.forename: Xiaohu
authors.initials: X
authors.lastname: Song
authors.forename: Ana M
authors.initials: AM
authors.lastname: Serrano
authors.forename: M Elena
authors.initials: ME
authors.lastname: Fernández-Tresguerres
authors.forename: Susana
authors.initials: S
authors.lastname: Moreno-Díaz de la Espina
authors.forename: Ariel B
authors.initials: AB
authors.lastname: Lindner
authors.forename: Rafael
authors.initials: R
authors.lastname: Giraldo
mesh_terms: D000682:Amyloid / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D044085:Microfluidics; D008853:Microscopy; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D059008:Time-Lapse Imaging
chemical_list: D000682:Amyloid; D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins; D011994:Recombinant Proteins; C063842:dnaK protein, E coli