التفاصيل البيبلوغرافية
| العنوان: |
Metabolic adaptations of Leishmania donovani in relation to differentiation, drug resistance, and drug pressure. |
| المؤلفون: |
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 |
| المصدر: |
Molecular Microbiology; Oct2013, Vol. 90 Issue 2, p428-442, 15p |
| مصطلحات موضوعية: |
LEISHMANIA donovani, DRUG resistance, CLASSIFICATION of protozoa, BIOLOGICAL adaptation, ANTIMONIDES, OXIDATIVE stress, PROMASTIGOTE, PROTOZOA |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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