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- Title
Metabolic adaptations of Leishmania donovani in relation to differentiation, drug resistance, and drug pressure.
- Authors
Berg, Maya; Vanaerschot, Manu; Jankevics, Andris; Cuypers, Bart; Maes, Ilse; Mukherjee, Sandip; Khanal, Basudha; Rijal, Suman; Roy, Syamal; Opperdoes, Fred; Breitling, Rainer; Dujardin, Jean‐Claude
- Abstract
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 SbIII drug pressure.
- Subjects
LEISHMANIA donovani; DRUG resistance; CLASSIFICATION of protozoa; BIOLOGICAL adaptation; ANTIMONIDES; OXIDATIVE stress; PROMASTIGOTE; PROTOZOA
- Publication
Molecular Microbiology, 2013, Vol 90, Issue 2, p428
- ISSN
0950-382X
- Publication type
Article
- DOI
10.1111/mmi.12374