A1 Refereed original research article in a scientific journal

The Chaperonin TRiC/CCT Inhibitor HSF1A Protects Cells from Intoxication with Pertussis Toxin




AuthorsJia, Jinfang; Zoeschg, Manuel; Barth, Holger; Pulliainen, Arto T.; Ernst, Katharina

PublisherMPDI

Publication year2024

JournalToxins

Journal name in sourceToxins

Article number36

Volume16

Issue1

ISSN2072-6651

eISSN2072-6651

DOIhttps://doi.org/10.3390/toxins16010036

Web address https://www.mdpi.com/2072-6651/16/1/36

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/381117455


Abstract
Pertussis toxin (PT) is a bacterial AB5-toxin produced by Bordetella pertussis and a major molecular determinant of pertussis, also known as whooping cough, a highly contagious respiratory disease. In this study, we investigate the protective effects of the chaperonin TRiC/CCT inhibitor, HSF1A, against PT-induced cell intoxication. TRiC/CCT is a chaperonin complex that facilitates the correct folding of proteins, preventing misfolding and aggregation, and maintaining cellular protein homeostasis. Previous research has demonstrated the significance of TRiC/CCT in the functionality of the Clostridioides difficile TcdB AB-toxin. Our findings reveal that HSF1A effectively reduces the levels of ADP-ribosylated Gαi, the specific substrate of PT, in PT-treated cells, without interfering with enzyme activity in vitro or the cellular binding of PT. Additionally, our study uncovers a novel interaction between PTS1 and the chaperonin complex subunit CCT5, which correlates with reduced PTS1 signaling in cells upon HSF1A treatment. Importantly, HSF1A mitigates the adverse effects of PT on cAMP signaling in cellular systems. These results provide valuable insights into the mechanisms of PT uptake and suggest a promising starting point for the development of innovative therapeutic strategies to counteract pertussis toxin-mediated pathogenicity.

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Last updated on 2025-10-02 at 14:14