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Genetic defects affecting the development of severe Buruli Ulcer

ABSTRACT: Genetic defects affecting the development of severe Buruli Ulcer

PROVIDER: PRJNA451353 | ENA |

REPOSITORIES: ENA

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Genetic defects affecting the development of severe Buruli Ulcer

Project description:Buruli ulcer (BU) is a tropical infectious disease caused by Mycobacterium ulcerans. BU causes profound skin ulcerations and eventually bone infections. Life-long functional sequelae are observed in more than 20% of patients, most of whom are children. Several observations, in particular the large variability in the clinical severity of the disease after infection, suggested the role of human genetic factors in the development of BU. Here, we report two children with severe BU, born of consanguineous parents. The deep genetic exploration of this family led to the identification of a small deletion on chromosome 8 in both patients. The corresponding article is in press in PloS Neglected Tropical Diseases

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Transcriptomics in whole-blood cells of Buruli ulcer patients identifies a signature of inflammation

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.

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Project description:Microbiome samples derived from Buruli ulcer wounds and non-Buruli ulcer skin ulcerations

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Project description:The causal agent of Buruli ulcer

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Transcriptomics in whole-blood cells of Buruli ulcer patients identifies a signature of inflammation

Project description:Transcriptomics in whole-blood cells of Buruli ulcer patients identifies a signature of inflammation

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Genome-wide analysis of long noncoding RNA expression profile in patients with Marjolin’s ulcer

Project description:Marjolin’s Ulcer is an aggressive cutaneous malignancy that typically ensues over a period of time in the post-burned lesions and scars or any other chronic wound. Marjolin’s Ulcer makes up 1.2% of all skin cancers, it is reported that 2% of squamous cell carcinoma and 0.03% of basal cell carcinoma originate in burn scars. Recent studies have shown that long non-coding (lncRNA) plays critical roles in a myriad of biological processes and human diseases,Since the roles of lncRNA in Marjolin’s Ulcer remain unknown,they were investigated in the study.Our findings indicate that the expression profiles of lncRNAs has changed in Marjolin’s Ulcer as compared with normal skin and para-cancerous scar, and may provide novel insight into the molecular mechanism underlying the disease and potential novel diagnostic or therapeutic targets for Marjolin’s Ulcer.

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Mycobacterium ulcerans

Project description:Causative agent of Buruli and Bairnsdale ulcer

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