Adaptation mechanisms of Clostridioides difficile to auranofin and its impact on human gut microbiota.

Autor: Anjou C; Institut Pasteur, Université Paris Cité, UMR CNRS 6047, Laboratoire Pathogenèse des Bactéries Anaérobies, F-75015, Paris, France., Royer M; Institut Pasteur, Université Paris Cité, UMR CNRS 6047, Laboratoire Pathogenèse des Bactéries Anaérobies, F-75015, Paris, France.; Institut Pasteur, Université Paris Cité, UMR CNRS 6047, Unité Écologie et Évolution de la Résistance aux Antibiotiques, Paris, France., Bertrand É; Institut Pasteur, Université Paris Cité, UMR CNRS 6047, Laboratoire Pathogenèse des Bactéries Anaérobies, F-75015, Paris, France., Bredon M; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, Paris, France.; Paris Center for Microbiome Medicine (PaCeMM) FHU, Paris, France., Le Bris J; Microbial Evolutionary Genomics, Institut Pasteur, CNRS UMR3525, Université Paris Cité, Paris, France.; Sorbonne Université, Collège Doctoral, École Doctorale Complexité du Vivant, 75005, Paris, France., Salgueiro IA; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, Paris, France.; Paris Center for Microbiome Medicine (PaCeMM) FHU, Paris, France., Caulat LC; Institut Pasteur, Université Paris Cité, UMR CNRS 6047, Laboratoire Pathogenèse des Bactéries Anaérobies, F-75015, Paris, France., Dupuy B; Institut Pasteur, Université Paris Cité, UMR CNRS 6047, Laboratoire Pathogenèse des Bactéries Anaérobies, F-75015, Paris, France., Barbut F; Université Paris Cité, INSERM, UMR-1139, Paris, France.; National Reference Laboratory for C. difficile, Assistance Publique Hôpitaux de Paris, Hôpital Saint-Antoine, 75012, Paris, France., Morvan C; Institut Pasteur, Université Paris Cité, UMR CNRS 6047, Laboratoire Pathogenèse des Bactéries Anaérobies, F-75015, Paris, France., Rolhion N; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, CRSA, Paris, France.; Paris Center for Microbiome Medicine (PaCeMM) FHU, Paris, France., Martin-Verstraete I; Institut Pasteur, Université Paris Cité, UMR CNRS 6047, Laboratoire Pathogenèse des Bactéries Anaérobies, F-75015, Paris, France. isabelle.martin-verstraete@pasteur.fr.; Institut Universitaire de France, Paris, France. isabelle.martin-verstraete@pasteur.fr.
Jazyk: angličtina
Zdroj: NPJ biofilms and microbiomes [NPJ Biofilms Microbiomes] 2024 Sep 17; Vol. 10 (1), pp. 86. Date of Electronic Publication: 2024 Sep 17.
DOI: 10.1038/s41522-024-00551-3
Abstrakt: Auranofin (AF), a former rheumatoid polyarthritis treatment, gained renewed interest for its use as an antimicrobial. AF is an inhibitor of thioredoxin reductase (TrxB), a thiol and protein repair enzyme, with an antibacterial activity against several bacteria including C. difficile, an enteropathogen causing post-antibiotic diarrhea. Several studies demonstrated the effect of AF on C. difficile physiology, but the crucial questions of resistance mechanisms and impact on microbiota remain unaddressed. We explored potential resistance mechanisms by studying the impact of TrxB multiplicity and by generating and characterizing adaptive mutations. We showed that if mutants inactivated for trxB genes have a lower MIC of AF, the number of TrxBs naturally present in clinical strains does not impact the MIC. All stable mutations isolated after AF long-term exposure were in the anti-sigma factor of σ B and strongly affect physiology. Finally, we showed that AF has less impact on human gut microbiota than vancomycin.
(© 2024. The Author(s).)
Databáze: MEDLINE
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