Untargeted metabolomics to understand the basis of phenotypic differences in amphotericin B-resistant Leishmania parasites

Wellcome Open Research
Andrew W Pountain, Michael Barrett

Abstract

Background: Protozoan Leishmania parasites are responsible for a range of clinical infections that represent a substantial challenge for global health. Amphotericin B (AmB) is increasingly used to treat Leishmania infection, so understanding the potential for resistance to this drug is an important priority. Previously we described four independently-derived AmB-resistant L. mexicana lines that exhibited resistance-associated genetic lesions resulting in altered sterol content. However, substantial phenotypic variation between these lines, including differences in virulence attributes, were not fully explained by these changes. Methods: To identify alterations in cellular metabolism potentially related to phenotypic differences between wild-type and AmB-resistant lines, we extracted metabolites and performed untargeted metabolomics by liquid chromatography-mass spectrometry. Results: We observed substantial differences in metabolite abundance between lines, arising in an apparently stochastic manner. Concerted remodeling of central carbon metabolism was not observed; however, in three lines, decreased abundance of several oligohexoses was observed. Given that the oligomannose mannogen is an important virulence factor in Leishma...Continue Reading

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Citations

Jun 27, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Andrea MedeirosMarcelo A Comini
Sep 3, 2021·PLoS Neglected Tropical Diseases·Peerut ChienwichaiOnrapak Reamtong

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