Regulation of mycolactone, the Mycobacterium ulcerans toxin, depends on nutrient source.
BACKGROUND: Mycobacterium ulcerans, a slow-growing environmental bacterium, is the etiologic agent of Buruli ulcer, a necrotic skin disease. Skin lesions are caused by mycolactone, the main virulence factor of M. ulcerans, with dermonecrotic (destruction of the skin and soft tissues) and immunosuppr...
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ftdoajarticles:oai:doaj.org/article:a921efd8b48242c3bab789e0d9b9a320 2023-05-15T15:11:43+02:00 Regulation of mycolactone, the Mycobacterium ulcerans toxin, depends on nutrient source. Caroline Deshayes Shiva Kumar Angala Estelle Marion Irène Brandli Jérémie Babonneau Laurent Preisser Sara Eyangoh Yves Delneste Pierre Legras Chantal De Chastellier Timothy P Stinear Mary Jackson Laurent Marsollier 2013-11-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002502 https://doaj.org/article/a921efd8b48242c3bab789e0d9b9a320 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3828164?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002502 https://doaj.org/article/a921efd8b48242c3bab789e0d9b9a320 PLoS Neglected Tropical Diseases, Vol 7, Iss 11, p e2502 (2013) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2013 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002502 2022-12-31T02:16:11Z BACKGROUND: Mycobacterium ulcerans, a slow-growing environmental bacterium, is the etiologic agent of Buruli ulcer, a necrotic skin disease. Skin lesions are caused by mycolactone, the main virulence factor of M. ulcerans, with dermonecrotic (destruction of the skin and soft tissues) and immunosuppressive activities. This toxin is secreted in vesicles that enhance its biological activities. Nowadays, it is well established that the main reservoir of the bacilli is localized in the aquatic environment where the bacillus may be able to colonize different niches. Here we report that plant polysaccharides stimulate M. ulcerans growth and are implicated in toxin synthesis regulation. METHODOLOGY/PRINCIPAL FINDINGS: In this study, by selecting various algal components, we have identified plant-specific carbohydrates, particularly glucose polymers, capable of stimulating M. ulcerans growth in vitro. Furthermore, we underscored for the first time culture conditions under which the polyketide toxin mycolactone, the sole virulence factor of M. ulcerans identified to date, is down-regulated. Using a quantitative proteomic approach and analyzing transcript levels by RT-qPCR, we demonstrated that its regulation is not at the transcriptional or translational levels but must involve another type of regulation. M. ulcerans produces membrane vesicles, as other mycobacterial species, in which are the mycolactone is concentrated. By transmission electron microscopy, we observed that the production of vesicles is independent from the toxin production. Concomitant with this observed decrease in mycolactone production, the production of mycobacterial siderophores known as mycobactins was enhanced. CONCLUSIONS/SIGNIFICANCE: This work is the first step in the identification of the mechanisms involved in mycolactone regulation and paves the way for the discovery of putative new drug targets in the future. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 7 11 e2502 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Caroline Deshayes Shiva Kumar Angala Estelle Marion Irène Brandli Jérémie Babonneau Laurent Preisser Sara Eyangoh Yves Delneste Pierre Legras Chantal De Chastellier Timothy P Stinear Mary Jackson Laurent Marsollier Regulation of mycolactone, the Mycobacterium ulcerans toxin, depends on nutrient source. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND: Mycobacterium ulcerans, a slow-growing environmental bacterium, is the etiologic agent of Buruli ulcer, a necrotic skin disease. Skin lesions are caused by mycolactone, the main virulence factor of M. ulcerans, with dermonecrotic (destruction of the skin and soft tissues) and immunosuppressive activities. This toxin is secreted in vesicles that enhance its biological activities. Nowadays, it is well established that the main reservoir of the bacilli is localized in the aquatic environment where the bacillus may be able to colonize different niches. Here we report that plant polysaccharides stimulate M. ulcerans growth and are implicated in toxin synthesis regulation. METHODOLOGY/PRINCIPAL FINDINGS: In this study, by selecting various algal components, we have identified plant-specific carbohydrates, particularly glucose polymers, capable of stimulating M. ulcerans growth in vitro. Furthermore, we underscored for the first time culture conditions under which the polyketide toxin mycolactone, the sole virulence factor of M. ulcerans identified to date, is down-regulated. Using a quantitative proteomic approach and analyzing transcript levels by RT-qPCR, we demonstrated that its regulation is not at the transcriptional or translational levels but must involve another type of regulation. M. ulcerans produces membrane vesicles, as other mycobacterial species, in which are the mycolactone is concentrated. By transmission electron microscopy, we observed that the production of vesicles is independent from the toxin production. Concomitant with this observed decrease in mycolactone production, the production of mycobacterial siderophores known as mycobactins was enhanced. CONCLUSIONS/SIGNIFICANCE: This work is the first step in the identification of the mechanisms involved in mycolactone regulation and paves the way for the discovery of putative new drug targets in the future. |
format |
Article in Journal/Newspaper |
author |
Caroline Deshayes Shiva Kumar Angala Estelle Marion Irène Brandli Jérémie Babonneau Laurent Preisser Sara Eyangoh Yves Delneste Pierre Legras Chantal De Chastellier Timothy P Stinear Mary Jackson Laurent Marsollier |
author_facet |
Caroline Deshayes Shiva Kumar Angala Estelle Marion Irène Brandli Jérémie Babonneau Laurent Preisser Sara Eyangoh Yves Delneste Pierre Legras Chantal De Chastellier Timothy P Stinear Mary Jackson Laurent Marsollier |
author_sort |
Caroline Deshayes |
title |
Regulation of mycolactone, the Mycobacterium ulcerans toxin, depends on nutrient source. |
title_short |
Regulation of mycolactone, the Mycobacterium ulcerans toxin, depends on nutrient source. |
title_full |
Regulation of mycolactone, the Mycobacterium ulcerans toxin, depends on nutrient source. |
title_fullStr |
Regulation of mycolactone, the Mycobacterium ulcerans toxin, depends on nutrient source. |
title_full_unstemmed |
Regulation of mycolactone, the Mycobacterium ulcerans toxin, depends on nutrient source. |
title_sort |
regulation of mycolactone, the mycobacterium ulcerans toxin, depends on nutrient source. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pntd.0002502 https://doaj.org/article/a921efd8b48242c3bab789e0d9b9a320 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 7, Iss 11, p e2502 (2013) |
op_relation |
http://europepmc.org/articles/PMC3828164?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002502 https://doaj.org/article/a921efd8b48242c3bab789e0d9b9a320 |
op_doi |
https://doi.org/10.1371/journal.pntd.0002502 |
container_title |
PLoS Neglected Tropical Diseases |
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7 |
container_issue |
11 |
container_start_page |
e2502 |
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1766342528642056192 |