Berg, M. et al. (2013) Metabolic adaptations of Leishmania donovaniin relation to differentiation, drug resistance, and drug pressure. Molecular Microbiology, 90(2), pp. 428-442. (doi: 10.1111/mmi.12374)
Full text not currently available from Enlighten.
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.
Item Type: | Articles |
---|---|
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Breitling, Professor Rainer |
Authors: | Berg, M., Vanaerschot, M., Jankevics, A., Cuypers, B., Maes, I., Mukherjee, S., Khanal, B., Rijal, S., Roy, S., Opperdoes, F., Breitling, R., and Dujardin, J. |
College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
Journal Name: | Molecular Microbiology |
ISSN: | 0950-382X |
ISSN (Online): | 1365-2958 |
University Staff: Request a correction | Enlighten Editors: Update this record