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© Emmanuel Lemichez
Microscopy image showing the formation of large tunnels in a blood vessel endothelial cell induced by a group of bacterial toxins
Publication : Scientific reports

Hsp70 facilitates trans-membrane transport of bacterial ADP-ribosylating toxins into the cytosol of mammalian cells

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Scientific reports - 02 Jun 2017

Ernst K, Schmid J, Beck M, Hägele M, Hohwieler M, Hauff P, Ückert AK, Anastasia A, Fauler M, Jank T, Aktories K, Popoff MR, Schiene-Fischer C, Kleger A, Müller M, Frick M, Barth H

Link to Pubmed [PMID] – 28578412

Sci Rep 2017 Jun;7(1):2724

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.

https://www.ncbi.nlm.nih.gov/pubmed/28578412