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From Bacterial Toxin to Therapeutic Agent: The Unexpected Fate of Mycolactone

“Recognizing a surprising fact is the first step towards discovery.” This famous quote from Louis Pasteur is particularly appropriate to describe what led us to study mycolactone, a lipid toxin produced by the human pathogen Mycobacterium ulcerans. M. ulcerans is the causative agent of Buruli ulcer,...

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Detalles Bibliográficos
Autores principales: Ricci, Daniela, Demangel, Caroline
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10303314/
https://www.ncbi.nlm.nih.gov/pubmed/37368670
http://dx.doi.org/10.3390/toxins15060369
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author Ricci, Daniela
Demangel, Caroline
author_facet Ricci, Daniela
Demangel, Caroline
author_sort Ricci, Daniela
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description “Recognizing a surprising fact is the first step towards discovery.” This famous quote from Louis Pasteur is particularly appropriate to describe what led us to study mycolactone, a lipid toxin produced by the human pathogen Mycobacterium ulcerans. M. ulcerans is the causative agent of Buruli ulcer, a neglected tropical disease manifesting as chronic, necrotic skin lesions with a “surprising” lack of inflammation and pain. Decades after its first description, mycolactone has become much more than a mycobacterial toxin. This uniquely potent inhibitor of the mammalian translocon (Sec61) helped reveal the central importance of Sec61 activity for immune cell functions, the spread of viral particles and, unexpectedly, the viability of certain cancer cells. We report in this review the main discoveries that marked our research into mycolactone, and the medical perspectives they opened up. The story of mycolactone is not over and the applications of Sec61 inhibition may go well beyond immunomodulation, viral infections, and oncology.
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spelling pubmed-103033142023-06-29 From Bacterial Toxin to Therapeutic Agent: The Unexpected Fate of Mycolactone Ricci, Daniela Demangel, Caroline Toxins (Basel) Review “Recognizing a surprising fact is the first step towards discovery.” This famous quote from Louis Pasteur is particularly appropriate to describe what led us to study mycolactone, a lipid toxin produced by the human pathogen Mycobacterium ulcerans. M. ulcerans is the causative agent of Buruli ulcer, a neglected tropical disease manifesting as chronic, necrotic skin lesions with a “surprising” lack of inflammation and pain. Decades after its first description, mycolactone has become much more than a mycobacterial toxin. This uniquely potent inhibitor of the mammalian translocon (Sec61) helped reveal the central importance of Sec61 activity for immune cell functions, the spread of viral particles and, unexpectedly, the viability of certain cancer cells. We report in this review the main discoveries that marked our research into mycolactone, and the medical perspectives they opened up. The story of mycolactone is not over and the applications of Sec61 inhibition may go well beyond immunomodulation, viral infections, and oncology. MDPI 2023-05-30 /pmc/articles/PMC10303314/ /pubmed/37368670 http://dx.doi.org/10.3390/toxins15060369 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Ricci, Daniela
Demangel, Caroline
From Bacterial Toxin to Therapeutic Agent: The Unexpected Fate of Mycolactone
title From Bacterial Toxin to Therapeutic Agent: The Unexpected Fate of Mycolactone
title_full From Bacterial Toxin to Therapeutic Agent: The Unexpected Fate of Mycolactone
title_fullStr From Bacterial Toxin to Therapeutic Agent: The Unexpected Fate of Mycolactone
title_full_unstemmed From Bacterial Toxin to Therapeutic Agent: The Unexpected Fate of Mycolactone
title_short From Bacterial Toxin to Therapeutic Agent: The Unexpected Fate of Mycolactone
title_sort from bacterial toxin to therapeutic agent: the unexpected fate of mycolactone
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10303314/
https://www.ncbi.nlm.nih.gov/pubmed/37368670
http://dx.doi.org/10.3390/toxins15060369
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