Heterogeneity of Mycolactones Produced by Clinical Isolates of Mycobacterium ulcerans : Implications for Virulence
| العنوان: | Heterogeneity of Mycolactones Produced by Clinical Isolates of Mycobacterium ulcerans : Implications for Virulence |
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| المؤلفون: | Richard E. Lee, Françoise Portaels, Armand Mve-Obiang, Pamela L. C. Small |
| المصدر: | Infection and Immunity. 71:774-783 |
| بيانات النشر: | American Society for Microbiology, 2003. |
| سنة النشر: | 2003 |
| مصطلحات موضوعية: | Buruli ulcer, Bacterial Toxins, Immunology, Mycobacterium Infections, Nontuberculous, Virulence, Biology, medicine.disease_cause, Microbiology, Mass Spectrometry, Cell Line, Mice, chemistry.chemical_compound, Polyketide, medicine, Animals, Humans, Mycolactone, Mycobacterium ulcerans, Toxin, Biological activity, Fibroblasts, medicine.disease, biology.organism_classification, Molecular Pathogenesis, Virology, Infectious Diseases, chemistry, Parasitology, Chromatography, Thin Layer, Macrolides, Bacteria |
| الوصف: | Mycobacterium ulcerans is the causative agent of Buruli ulcer, a severe necrotizing skin disease endemic in tropical countries. Clinical evidence suggests that M. ulcerans isolates from Asia, Mexico, and Australia may be less virulent than isolates from Africa. In vivo studies suggest that mycolactone, a polyketide-derived macrolide toxin, plays a major role in the tissue destruction and immune suppression which occur in cases of Buruli ulcer. Mycolactones were extracted from 34 isolates of M. ulcerans representing strains from Africa, Malaysia, Asia, Australia, and Mexico. Thin-layer chromatography, mass spectroscopic analysis, and cytopathic assays of partially purified mycolactones from these isolates revealed that M. ulcerans produces a heterogeneous mixture of mycolactone variants. Mycolactone A/B, the most biologically active mycolactone species, was identified by mass spectroscopy as [M + Na] + at m/z 765.5 in all cytotoxic isolates except for those from Mexico. Mycolactone C [M+Na] + at m/z 726.3 was the dominant mycolactone species in eight Australian isolates, and mycolactone D [M+Na] + m/z 781.2 was characteristic of two Asian strains. Mycolactone species are conserved within specific geographic areas, suggesting that there may be a correlation between mycolactone profile and virulence. In addition, the core lactone, [M+Na] + m/z 447.4, was identified as a minor species, supporting the hypothesis that mycolactones are synthesized by two polyketide synthases. A cytopathic assay of the core lactone showed that this molecule is sufficient for cytotoxicity, although it is much less potent than the complete mycolactone. |
| تدمد: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.71.2.774-783.2003 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1f0020f09cf38ea3393eb63ace29b006 https://doi.org/10.1128/iai.71.2.774-783.2003 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1f0020f09cf38ea3393eb63ace29b006 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10985522 00199567 |
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| DOI: | 10.1128/iai.71.2.774-783.2003 |