| Autor: |
Maya, Berg, Manu, Vanaerschot, Andris, Jankevics, Bart, Cuypers, Ilse, Maes, Sandip, Mukherjee, Basudha, Khanal, Suman, Rijal, Syamal, Roy, Fred, Opperdoes, Rainer, Breitling, Jean-Claude, Dujardin |
| Rok vydání: |
2013 |
| Předmět: |
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| Zdroj: |
Molecular microbiology. 90(2) |
| ISSN: |
1365-2958 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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