2 research outputs found

    Direct assessment in bacteria of prionoid propagation and phenotype selection by Hsp70 chaperone

    Get PDF
    26 p.-9 fig.-11 sup. fig.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. © 2014 John Wiley & Sons Ltd.This work has been supported by grants of the Agence Nationale de la Recherche France,Institut National de la Santé et de la RechercheMédicale–Institut National de Recherche en Informatique et en Automatique projet d’envergure and Axa Foundation Chair on Longevity to A.B.L.; and from Spanish MINECO (BIO2009-06952 and CSD2009-00088) to R.G.Peer reviewe
    corecore