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Title
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Metabolic adaptations of Leishmania donovani in relation to differentiation, drug resistance, and drug pressure
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Author
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Abstract
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| Antimonial (sodium stibogluconate, SSG) resistance and differentiation have been shown to be closely linked in Leishmania donovani, with SSG-resistant strains showing an increased capacity to generate infectious (metacyclic) forms. This is the first untargeted LC-MS metabolomics study which integrated both phenomena in one experimental design and provided insights into metabolic differences between three clinical L.donovani strains with a similar genetic background but different SSG-susceptibilities. We performed this analysis at different stages during promastigote growth and in the absence or presence of drug pressure. When comparing SSG-resistant and SSG-sensitive strains, a number of metabolic changes appeared to be constitutively present in all growth stages, pointing towards a clear link with SSG-resistance, whereas most metabolic changes were only detected in the stationary stage. These changes reflect the close intertwinement between SSG-resistance and an increased metacyclogenesis in resistant parasites. The metabolic changes suggest that SSG-resistant parasites have (i) an increased capacity for protection against oxidative stress; (ii) a higher fluidity of the plasma membrane; and (iii) a metabolic survival kit to better endure infection. These changes were even more pronounced in a resistant strain kept under Sb-III drug pressure. |
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Language
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English
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Source (journal)
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Molecular microbiology. - Oxford
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Publication
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Oxford
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2013
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ISSN
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0950-382X
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DOI
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10.1111/MMI.12374
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Volume/pages
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90
:2
(2013)
, p. 428-442
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ISI
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000325486100017
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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