ArticleThe Journal of clinical investigation2013
Mycolactone activation of Wiskott-Aldrich syndrome proteins underpins Buruli ulcer formation.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- A need for null models in understanding disease transmission: the example of Mycobacterium ulcerans (Buruli ulcer disease).FEMS microbiology reviews · 2022Pooled it
- Aberrant stromal tissue factor localisation and mycolactone-driven vascular dysfunction, exacerbated by IL-1β, are linked to fibrin formation in Buruli ulcer lesions.PLoS pathogens · 2022Trial
- Modelling the cost-effectiveness of interventions to treat or prevent neuropathic ulcers arising from leprosy: application to L-PRF.Cost effectiveness and resource allocation : C/E · 2026Article
- Buruli ulcer.Nature reviews. Disease primers · 2025Review
- Micronutrient-deficient diets and possible environmental enteric dysfunction in Buruli ulcer endemic communities in Ghana: Lower dietary diversity and reduced serum zinc and vitamin C implicate micronutrient status a possible susceptibility factor.PLoS neglected tropical diseases · 2025Article
- TheeLife · 2025Article
- Nuclear N-WASP Induces Actin Polymerization in the Nucleus with Cortactin as an Essential Factor.Cells · 2025Article
- Review
- Mycolactone causes destructive Sec61-dependent loss of the endothelial glycocalyx and vessel basement membrane: a new indirect mechanism driving tissue necrosis inbioRxiv : the preprint server for biology · 2024Article
- Article
- Article
- Genome-wide screening identified SEC61A1 as an essential factor for mycolactone-dependent apoptosis in human premonocytic THP-1 cells.PLoS neglected tropical diseases · 2022Article
- A glycine-rich PE_PGRS protein governs mycobacterial actin-based motility.Nature communications · 2022Article
- Article
- Conditions for Handling and Optimal Storage of Mycolactone.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Induced Synthesis of Mycolactone Restores the Pathogenesis ofFrontiers in immunology · 2022Article
- Mycolactone enhances the Ca2+ leak from endoplasmic reticulum by trapping Sec61 translocons in a Ca2+ permeable state.The Biochemical journal · 2021Article
- Responses to chemical cross-talk between the Mycobacterium ulcerans toxin, mycolactone, and Staphylococcus aureus.Scientific reports · 2021Article
- Article
- Molecular Mechanisms Underpinning the Circulation and Cellular Uptake ofFrontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
14 authors at 8 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mycolactone is a diffusible lipid secreted by the human pathogen Mycobacterium ulcerans, which induces the formation of open skin lesions referred to as Buruli ulcers. Here, we show that mycolactone operates by hijacking the Wiskott-Aldrich syndrome protein (WASP) family of actin-nucleating factors. By disrupting WASP autoinhibition, mycolactone leads to uncontrolled activation of ARP2/3-mediated assembly of actin in the cytoplasm. In epithelial cells, mycolactone-induced stimulation of ARP2/3 concentrated in the perinuclear region, resulting in defective cell adhesion and directional migration. In vivo injection of mycolactone into mouse ears consistently altered the junctional organization and stratification of keratinocytes, leading to epidermal thinning, followed by rupture. This degradation process was efficiently suppressed by coadministration of the N-WASP inhibitor wiskostatin. These results elucidate the molecular basis of mycolactone activity and provide a mechanism for Buruli ulcer pathogenesis. Our findings should allow for the rationale design of competitive inhibitors of mycolactone binding to N-WASP, with anti-Buruli ulcer therapeutic potential.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.