Metabolomic profiles delineate mycolactone signature in Buruli ulcer disease
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Date
2015-12-04
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Journal ISSN
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Publisher
Scientific Reports
Abstract
Infection of human skin with Mycobacterium ulcerans, the causative agent of Buruli ulcer, is
associated with the systemic diffusion of a bacterial macrolide named mycolactone. Patients with
progressive disease show alterations in their serum proteome, likely reflecting the inhibition of
secreted protein production by mycolactone at the cellular level. Here, we used semi-quantitative
metabolomics to characterize metabolic perturbations in serum samples of infected individuals, and
human cells exposed to mycolactone. Among the 430 metabolites profiled across 20 patients and 20
healthy endemic controls, there were significant differences in the serum levels of hexoses, steroid
hormones, acylcarnitines, purine, heme, bile acids, riboflavin and lysolipids. In parallel, analysis of
292 metabolites in human T cells treated or not with mycolactone showed alterations in hexoses,
lysolipids and purine catabolites. Together, these data demonstrate that M. ulcerans infection causes
systemic perturbations in the serum metabolome that can be ascribed to mycolactone. Of particular
importance to Buruli ulcer pathogenesis is that changes in blood sugar homeostasis in infected
patients are mirrored by alterations in hexose metabolism in mycolactone-exposed cells.
Description
An article published by Scientific Reports and available at DOI: 10.1038/srep17693
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Citation
Scientific Reports | 5:17693 | DOI: 10.1038/srep17693