Mycobacterium ulcerans Agy99
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ABSTRACT:
PROVIDER: PRJNA16230 | ENA |
REPOSITORIES: ENA
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Project description:Causative agent of Buruli and Bairnsdale ulcer
| PRJNA15695 | ENA
Project description:Mycobacterium ulcerans is the causal agent of Buruli ulcer, a chronic infectious disease and the third most common mycobacterial disease worldwide. Without early treatment, M. ulcerans provokes massive skin ulcers, caused by the mycolactone toxin, its main virulence factor. However, spontaneous healing may occur in Buruli ulcer patients several months or years after the disease onset. We have shown, in an original mouse model, that bacterial load remains high and viable in spontaneously healed tissues, suggesting that M. ulcerans switches to low levels of mycolactone production, adapting its strategy to survive in such a hostile environment. We investigated the regulation of mycolactone production, by using an RNA-seq strategy to study bacterial adaptation within our original mouse model of spontaneous healing. Pathway analysis and characterization of the tissue environment showed that the bacillus adapted to its new environment by modifying its metabolic activity and switching nutrient sources. Thus, M. ulcerans ensures its survival in healing tissues by reducing its secondary metabolism, leading to an inhibition of mycolactone synthesis and changes in cell wall composition. These findings shed new light on mycolactone regulation and pave the way for new therapeutic strategies.
2021-05-17 | GSE157956 | GEO
Project description:Comparative genomics reveals diversity and spatial clustering of Mycobacterium ulcerans in a small Buruli ulcer endemic area of West-Africa
| PRJNA499075 | ENA
Project description:Mycolactone, a lipid-like toxin, is the major virulence factor of Mycobacterium ulcerans, the etiological agent of Buruli ulcer. Its involvement in lesions development has been widely described in early stages of the disease, through its cytotoxic and immunosuppressive activities, but less is known about later stages. Here, we revisit the role of mycolactone in disease outcome and provide the first demonstration of the pro-inflammatory potential of this toxin. We found that the mycolactone-containing mycobacterial extracellular vesicles produced by M. ulcerans induced the production of IL-1β, a potent pro-inflammatory cytokine, in a TLR2-dependent manner, targeting NLRP3/1 inflammasomes. We showed our data to be relevant in a physiological context. The in vivo injection of these mycolactone-containing vesicles induced a strong local inflammatory response and tissue damages, which were prevented by corticosteroids. Finally, several soluble pro-inflammatory factors, including IL-1β, were detected in infected tissues from mice and Buruli ulcer patients. Our results revisit Buruli ulcer pathophysiology by giving a new insight, thus paving the way for development of new therapeutic strategies, taking account the pro-inflammatory potential of mycolactone.
2020-12-29 | GSE157350 | GEO
Project description:Mycobacterium ulcerans population genomics to inform on the spread of Buruli ulcer across central Africa
| PRJEB30333 | ENA
Project description:The drivers of tissue necrosis in Mycobacterium ulcerans infection (Buruli ulcer disease) have historically been ascribed solely to the cytotoxic action of the diffusible endotoxin, mycolactone. However, clinical evidence supporting a strong vascular contribution to disease aetiology has, until recently, been under-explored. We have now dissected mycolactone’s effects on primary vascular endothelial cells in vitro and in vivo. We show that mycolactone’s effect on endothelial morphology, adhesion, migration, and permeability are dependent on its action at the Sec61 translocon. Unbiased quantitative proteomics identified a profound effect on proteoglycans, driven both by a rapid loss of type II transmembrane proteins of the Golgi, including enzymes required for glycosaminoglycan (GAG) synthesis and the core proteins themselves. Loss of the glycocalyx is likely to be of particular mechanistic importance, since knockdown of galactosyltransferase II (beta-1,3-galactotransferase 6; B3Galt6), the GAG linker-building enzyme, phenocopied the permeability and phenotypic changes induced by mycolactone. Additionally, mycolactone depleted many secreted basement membrane components and microvascular basement membranes were disrupted in vivo. Remarkably, exogenous addition of laminin-511 reduced cell rounding, restored cell attachment and reversed the defective migration caused by mycolactone suggesting that this might be a viable therapeutic avenue in the future.
2025-01-14 | PXD037489 | Pride
Project description:Microbiome samples derived from Buruli ulcer wounds and non-Buruli ulcer skin ulcerations
| PRJEB14948 | ENA
Project description:The causal agent of bovine tuberculosis
| PRJEA18059 | ENA
Project description:Whether Mycobacterium ulcerans, the etiological agent of Buruli ulcer in numerous tropical countries, would exist in a dormant state as reported for closely related Mycobacterium species, has not been established. Six M. ulcerans strains were exposed to a progressive depletion in oxygen for 2 months, using the Wayne model of dormancy previously described for M. tuberculosis, and further examined by microscopy after staining of dynamic, dormant, and dead mycobacteria (DDD staining), microcalorimetry and subculture in the presence of dead and replicative M. ulcerans as controls. Mycobacterium ulcerans CU001 strain died during the progressive oxygen depletion and four of five remaining strains exhibited Nile red-stained intracellular lipid droplets and a 14- to 20-day regrowth when exposed to ambient air, consistent with dormancy. A fifth M. ulcerans 19423 strain stained negative in DDD staining and slowly regrew in 27 days. Three tested M. ulcerans strains yielded microcalorimetric pattern similar to that of the negative (dead) homologous controls, differing from that of the homologous positive (replicative) controls. The relevance of these experimental observations, suggesting a previously unreported dormancy state of M. ulcerans, warrants further investigations in the natural ecological niches where M. ulcerans thrive as well as in Buruli ulcer lesions.
| S-EPMC9294675 | biostudies-literature