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Demonstration of a protein with enhanced resistance to proteinase K in transmissible cytopathic condition elicited by cell-free lysate of free-living ameba Naegleria gruberi

Are microbial proteins capable of converting mammalian proteins into prion-like pathogens? A probable pathomechanism for some postinfectious degenerative sequelae and for natural prion disease in sheep, goat and cervids

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Abstract

The cell-free lysate of free-living amebae Naegleria gruberi and Naegleria fowleri were reported to elicit cytopathic effect in various cell lines that could be indefinitely transmitted by the culture media. The causative agent showed sensitivity to treatments detrimental to proteins while resisted exposures damaging to nucleic acids. Here we demonstrate that subsequent to exposure to N. gruberi lysate mild digestion with proteinase K reveals the presence of a protein band in HeLa cells absent from control cell lines. Though the small quantity of this protein with enhanced resistance to proteinase K relative to the total protein content of the sample has proved to date insufficient for its purification, we suppose that it is a human cellular protein that assumed altered conformation in a prion-like fashion. The conformational conversion could have been trigerred by an ameba protein in the lysate. In addition, we showed that HeLa cells treated with N. gruberi lysate display elevated cathepsin B activity which is assumed to be a secondary response to the accumulation of the proteinase K-resistant protein. We propose that a number of degenerative sequelae following previous microbial infections in mammals could have a similar pathomechanism. Moreover, epidemiological data strongly suggest that natural prion disease in sheep, goat and cervids may also have an etiology linked to prior infection/colonization with a microbe, as it had already been proposed by one of us.

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Acknowledgements

We thank Thelma D. Dunnebacke for her advice and Ákos Toth and Csaba Bognár for their excellent technical contributions. This study was funded by Diagon Ltd. Budapest, Hungary.

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  1. National Center for Epidemiology, Gyali út 2-6, 1097, Budapest, Hungary

    Miklos Füzi, Judit Pászti, Ágnes Gyuris, Erika Orosz, János Minárovits & Zsuzsa Szénási

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  1. Miklos Füzi
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  2. Judit Pászti
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  3. Ágnes Gyuris
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Correspondence to Miklos Füzi.

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Füzi, M., Pászti, J., Gyuris, Á. et al. Demonstration of a protein with enhanced resistance to proteinase K in transmissible cytopathic condition elicited by cell-free lysate of free-living ameba Naegleria gruberi . Struct Chem 19, 203–208 (2008). https://doi.org/10.1007/s11224-007-9273-8

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  • DOI: https://doi.org/10.1007/s11224-007-9273-8

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