ArticlePloS one2014
Stage-dependent expression and up-regulation of trypanothione synthetase in amphotericin B resistant Leishmania donovani.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 42 citations in OpenAlex.
- LC-MS Evaluation of the Redox Trypanothione Balance inAntioxidants (Basel, Switzerland) · 2025Article
- Genomic characterization of Leishmania (V.) braziliensis associated with antimony therapeutic failure and variable in vitro tolerance to amphotericin B.Scientific reports · 2025Article
- Putrescine Depletion inPathogens (Basel, Switzerland) · 2025Article
- Identification of Novel Antileishmanial Chemotypes By High-Throughput Virtual and In Vitro Screening.Acta parasitologica · 2024Article
- Repurposing of Food and Drug Admnistration (FDA) approved library to identify a potential inhibitor ofHeliyon · 2024Article
- Amphotericin B resistance in Leishmania mexicana: Alterations to sterol metabolism and oxidative stress response.PLoS neglected tropical diseases · 2022Article
- Polyamine Metabolism inMedical sciences (Basel, Switzerland) · 2022Review
- Effects of trypanocidal drugs on DNA synthesis: new insights into melarsoprol growth inhibition.Parasitology · 2021Article
- Article
- An overview of biochemically characterized drug targets in metabolic pathways of Leishmania parasite.Parasitology research · 2020Review
- Unravelling the proteomic signature of extracellular vesicles released by drug-resistant Leishmania infantum parasites.PLoS neglected tropical diseases · 2020Article
- Intraspecies differences in natural susceptibility to amphotericine B of clinical isolates of Leishmania subgenus Viannia.PloS one · 2018Article
- Deciphering the interplay between cysteine synthase and thiol cascade proteins in modulating Amphotericin B resistance and survival of Leishmania donovani under oxidative stress.Redox biology · 2017Article
- Article
- Intracellular zinc flux causes reactive oxygen species mediated mitochondrial dysfunction leading to cell death in Leishmania donovani.PloS one · 2017Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Kinetoplastids differ from other organisms in their ability to conjugate glutathione and spermidine to form trypanothione which is involved in maintaining redox homeostasis and removal of toxic metabolites. It is also involved in drug resistance, antioxidant mechanism, and defense against cellular oxidants. Trypanothione synthetase (TryS) of thiol metabolic pathway is the sole enzyme responsible for the biosynthesis of trypanothione in Leishmania donovani. In this study, TryS gene of L. donovani (LdTryS) was cloned, expressed, and fusion protein purified with affinity column chromatography. The purified protein showed optimum enzymatic activity at pH 8.0-8.5. The TryS amino acids sequences alignment showed that all amino acids involved in catalytic and ligands binding of L. major are conserved in L. donovani. Subcellular localization using digitonin fractionation and immunoblot analysis showed that LdTryS is localized in the cytoplasm. Furthermore, RT-PCR coupled with immunoblot analysis showed that LdTryS is overexpressed in Amp B resistant and stationary phase promastigotes (∼ 2.0-folds) than in sensitive strain and logarithmic phase, respectively, which suggests its involvement in Amp B resistance. Also, H2O2 treatment upto 150 µM for 8 hrs leads to 2-fold increased expression of LdTryS probably to cope up with oxidative stress generated by H2O2. Therefore, this study demonstrates stage- and Amp B sensitivity-dependent expression of LdTryS in L. donovani and involvement of TryS during oxidative stress to help the parasites survival.
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