Metabolic adaptations of Leishmania donovani in relation to differentiation, drug resistance, and drug pressure.
(2013) Molecular Microbiology — Vol. 90, n° 2, p. 428-442 (2013)
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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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Berg, M., Vanaerschot, M., Jankevics, A., Cuypers, B., Maes, I., Mukherjee, S., Khanal, B., Rijal, S., Roy, S., Opperdoes, F., Breitling, R., & Dujardin, J.-C. (2013). Metabolic adaptations of Leishmania donovani in relation to differentiation, drug resistance, and drug pressure. Molecular Microbiology, 90(2), 428-442. https://doi.org/10.1111/mmi.12374 (Original work published 2013)