Regulation of mycolactone, the Mycobacterium ulcerans toxin, depends on nutrient source
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 activ...
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Published in | PLoS neglected tropical diseases Vol. 7; no. 11; p. e2502 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
01.11.2013
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | 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.
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.
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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 Conceived and designed the experiments: CD TPS MJ LM. Performed the experiments: CD SKA EM IB JB PL LP. Analyzed the data: CD SE SKA CDC MJ LM. Contributed reagents/materials/analysis tools: YD CDC MJ LM EM LP. Wrote the paper: CD CDC MJ LM. The authors have declared that no competing interests exist. |
ISSN: | 1935-2735 1935-2727 1935-2735 |
DOI: | 10.1371/journal.pntd.0002502 |