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Journal articles
Hsp70 facilitates trans-membrane transport of bacterial ADP-ribosylating toxins into the cytosol of mammalian cells
Abstract : Binary enterotoxins Clostridium (C.) botulinum C2 toxin, C. perfringens iota toxin and C. difficile toxin CDT are composed of a transport (B) and a separate non-linked enzyme (A) component. Their B-components mediate endocytic uptake into mammalian cells and subsequently transport of the A-components from acidic endosomes into the cytosol, where the latter ADP-ribosylate G-actin resulting in cell rounding and cell death causing clinical symptoms. Protein folding enzymes, including Hsp90 and peptidyl-prolyl cis/trans isomerases facilitate transport of the A-components across endosomal membranes. Here, we identified Hsp70 as a novel host cell factor specifically interacting with A-components of C2, iota and CDT toxins to facilitate their transport into the cell cytosol. Pharmacological Hsp70-inhibition specifically prevented pH-dependent trans-membrane transport of A-components into the cytosol thereby protecting living cells and stem cell-derived human miniguts from intoxication. Thus, Hsp70-inhibition might lead to development of novel therapeutic strategies to treat diseases associated with bacterial ADP-ribosylating toxins.
Cited literature [70 references]
https://hal-pasteur.archives-ouvertes.fr/pasteur-01820496
Contributor : Floran Bidault Connect in order to contact the contributor
Submitted on : Thursday, June 21, 2018 - 5:14:30 PM
Last modification on : Thursday, January 6, 2022 - 12:22:02 PM
Contributor : Floran Bidault Connect in order to contact the contributor
Submitted on : Thursday, June 21, 2018 - 5:14:30 PM
Last modification on : Thursday, January 6, 2022 - 12:22:02 PM
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s41598-017-02882-y.pdf
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