ArticleScientific reports2021
Pharmacological targeting of host chaperones protects from pertussis toxin in vitro and in vivo.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 19 citations in OpenAlex.
- Novel endogenous protein-based strategies to inhibit clinically relevant bacterial AB-type toxins including pertussis toxin.Archives of toxicology · 2026Review
- The Battle Against Pertussis: Discovery of Endogenous Human Proteins and Peptides as Toxin-Inhibitors.Toxins · 2026Review
- An endogenous human peptide derived from αNaunyn-Schmiedeberg's archives of pharmacology · 2026Article
- The antiarrhythmic drugs amiodarone and dronedarone inhibit intoxication of cells with pertussis toxin.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Thioredoxin 1 moonlights as a chaperone for an interbacterial ADP-ribosyltransferase toxin.Nature communications · 2024Article
- The Chaperonin TRiC/CCT Inhibitor HSF1A Protects Cells from Intoxication with Pertussis Toxin.Toxins · 2024Article
- Cyclophilin inhibition as a strategy for the treatment of human disease.Frontiers in pharmacology · 2024Review
- Domperidone InhibitsToxins · 2023Article
- Inhibition of Pertussis Toxin by Human α-Defensins-1 and -5: Differential Mechanisms of Action.International journal of molecular sciences · 2023Article
- Domperidone Protects Cells from Intoxication withToxins · 2023Article
- Crystal structures of pertussis toxin with NADThe Journal of biological chemistry · 2022Article
- Exotoxin-Targeted Drug Modalities as Antibiotic Alternatives.ACS infectious diseases · 2022Review
- Novel Strategies to Inhibit Pertussis Toxin.Toxins · 2022Review
- Conquering the host:Frontiers in microbiology · 2022Review
- Requirement of Peptidyl-Prolyl Cis/Trans isomerases and chaperones for cellular uptake of bacterial AB-type toxins.Frontiers in cellular and infection microbiology · 2022Review
- Article
- Article
- Proline Isomerization as a Key Determinant for Hsp90-Toxin Interactions.Frontiers in cellular and infection microbiology · 2021Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
Abstract
Whooping cough is caused by Bordetella pertussis that releases pertussis toxin (PT) which comprises enzyme A-subunit PTS1 and binding/transport B-subunit. After receptor-mediated endocytosis, PT reaches the endoplasmic reticulum from where unfolded PTS1 is transported to the cytosol. PTS1 ADP-ribosylates G-protein α-subunits resulting in increased cAMP signaling. Here, a role of target cell chaperones Hsp90, Hsp70, cyclophilins and FK506-binding proteins for cytosolic PTS1-uptake is demonstrated. PTS1 specifically and directly interacts with chaperones in vitro and in cells. Specific pharmacological chaperone inhibition protects CHO-K1, human primary airway basal cells and a fully differentiated airway epithelium from PT-intoxication by reducing intracellular PTS1-amounts without affecting cell binding or enzyme activity. PT is internalized by human airway epithelium secretory but not ciliated cells and leads to increase of apical surface liquid. Cyclophilin-inhibitors reduced leukocytosis in infant mouse model of pertussis, indicating their promising potential for developing novel therapeutic strategies against whooping cough.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.