Metabolic adaptations of Leishmania donovani in relation to differentiation, drug resistance, and drug pressure
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Metabolic adaptations of Leishmania donovani in relation to
differentiation, drug resistance, and drug pressure
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| Creator |
Berg, Maya
Vanaerschot, Manu Cuypers, Bart Jankevics, Andris Mukherjee, Sandip Maes, Ilse Khanal, Basudha Rijal, Suman Roy, Syamal Opperdoes, Fred Breitling, Rainer Dujardin, Jean-Claude |
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| Subject |
Infectious Diseases and Immunology
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| Description |
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 SSGsusceptibilities.
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, anumber 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
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| Publisher |
Blackwell Publishing
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| Date |
2013
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/2429/1/MOLECULAR_MICROBIOLOGY__Volume__90____Issue__2____Pages__428%2D442_;2013.pdf
Berg, Maya and Vanaerschot, Manu and Cuypers, Bart and Jankevics, Andris and Mukherjee, Sandip and Maes, Ilse and Khanal, Basudha and Rijal, Suman and Roy, Syamal and Opperdoes, Fred and Breitling, Rainer and Dujardin, Jean-Claude (2013) Metabolic adaptations of Leishmania donovani in relation to differentiation, drug resistance, and drug pressure. Molecular Microbiology, 30 (2). pp. 428-442. |
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| Relation |
http://dx.doi.org/10.1111/mmi.12374
http://www.eprints.iicb.res.in/2429/ |
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