Alternativer Identifier:
-
Verwandter Identifier:
(Is Supplement To) 10.1080/19490976.2023.2256695 - DOI
Ersteller/in:
Papatheodorou, Panagiotis https://orcid.org/0000-0003-3571-695X [Institute of Experimental and Clinical Pharmacology, Toxicology and Pharmacology of Natural Products, Ulm University Medical Center]
Beitragende:
(Researcher)
Schumacher, Judith [Institute of Experimental and Clinical Pharmacology, Toxicology and Pharmacology of Natural Products, Ulm University Medical Center]

(Researcher)
Nienhaus, Astrid [Institute of Experimental and Clinical Pharmacology, Toxicology and Pharmacology of Natural Products, Ulm University Medical Center]

(Researcher)
Heber, Sebastian [Institute of Experimental and Clinical Pharmacology, Toxicology and Pharmacology of Natural Products, Ulm University Medical Center]

(Researcher)
Chaves-Olarte, Esteban https://orcid.org/0000-0002-4840-2426 [Centro de Investigación en Enfermedades Tropicales and Facultad de Microbiología, Universidad de Costa Rica]

(Researcher)
Rodríguez, César https://orcid.org/0000-0001-5599-0652 [Centro de Investigación en Enfermedades Tropicales and Facultad de Microbiología, Universidad de Costa Rica]

(Project Leader)
Barth, Holger https://orcid.org/0000-0002-2706-3402 [Institute of Experimental and Clinical Pharmacology, Toxicology and Pharmacology of Natural Products, Ulm University Medical Center]
Titel:
Schumacher et al (raw data)
Weitere Titel:
(Other) Exploring the inhibitory potential of the antiarrhythmic drug amiodarone against Clostridioides difficile toxins TcdA and TcdB
Beschreibung:
(Object) Zip file includes all figures of the Schumacher et al. manuscript with PDF files providing the original image data and Excel calculations that were used to generate the figures.
(Abstract) The intestinal pathogen Clostridioides difficile is the leading cause of antibiotic-associated diarrhea and pseudomembranous colitis in humans. The symptoms of C. difficile-associated diseases (CDADs) are directly associated with the pathogen’s toxins TcdA and TcdB, which enter host cells and inactivate Rho and/or Ras GTPases by glucosylation. Membrane cholesterol is crucial during the intoxication process of TcdA and TcdB, and likely involved during pore formation of both toxins in endosomal membranes, a key step after cellular uptake for the translocation of the glucosyltransferase domain of both toxins from endosomes into the host cell cytosol. The licensed drug amiodarone, a multichannel blocker commonly used in the treatment of cardiac dysrhythmias, is also capable of inhibiting endosomal acidification and, as shown recently, cholesterol biosynthesis. Thus, we were keen to investigate in vitro with cultured cells and human intestinal organoids, whether amiodarone preincubation protects from TcdA and/or TcdB intoxication. Amiodarone conferred protection against both toxins independently and in combination as well as against toxin variants from the clinically relevant, epidemic C. difficile strain NAP1/027. Further mechanistic studies suggested that amiodarone’s mode-of-inhibition involves also interference with the translocation pore of both toxins. Our study opens the possibility of repurposing the licensed drug amiodarone as a novel pan-variant antitoxin therapeutic in the context of CDADs.
Schlagworte:
Amiodarone
Clostridioides difficile infection
Toxin inhibitor
Drug repurposing
Drug repositioning
Membrane cholesterol
Zugehörige Informationen:
(2157) PubChem ID of amiodarone
(C25H29I2NO3) Molecular formular of amiodarone
(645.3) Molecular weigth of amiodarone
Sprache:
Englisch
Herausgeber/in:
Papatheodorou, Panagiotis
Erstellungsjahr:
Fachgebiet:
Medicine
Biochemistry
Biology
Chemistry
Life Science
Objekttyp:
(Collection) Raw data
Datenquelle:
-
Verwendete Software:
-
Datenverarbeitung:
-
Erscheinungsjahr:
Rechteinhaber/in:
Papatheodorou, Panagiotis

Schumacher, Judith

Barth, Holger
Förderung:
Deutsche Forschungsgemeinschaft - (BA 2087/8-1) Project number 450938962
Name Speichervolumen Metadaten Upload Aktion

Zugriffe der letzten sechs Monate

Aufrufe der Datenpaket-Seite

276


Downloads des Datenpakets

1


Gesamtstatistik

Zeitraum Aufrufe der Datenpaket-Seite Datenpaket heruntergeladen
Juni 2024 29 0
Mai 2024 46 0
Apr. 2024 64 0
März 2024 30 0
Feb. 2024 55 0
Jan. 2024 52 1
Vorher 176 4
Gesamt 452 5
Status:
Publiziert
Eingestellt von:
papascience
Erstellt am:
Archivierungsdatum:
2023-09-26
Archivgröße:
24,0 MB
Archiversteller:
papascience
Archiv-Prüfsumme:
50304b75a259aa022a08b9d758e95b4d (MD5)
Ende des Embargo-Zeitraums:
-