ArticleRedox biology2017
Deciphering the interplay between cysteine synthase and thiol cascade proteins in modulating Amphotericin B resistance and survival of Leishmania donovani under oxidative stress.
Article in Redox biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 64 citations in OpenAlex.
- Coumarin derivatives as new chemotype targeting leishmanial sterol biosynthesis pathway proteins: an integrated in vitro, mechanistic, and in silico evaluation.World journal of microbiology & biotechnology · 2026Article
- Deciphering the potentiality of Andrographolide derivatives against Pseudomonas aeruginosa: in vitro analysis and mechanistic insights.World journal of microbiology & biotechnology · 2026Article
- In Silico Targeting of Trypanothione Reductase and Glycerol-3-Phosphate Dehydrogenase inMicroorganisms · 2026Article
- High-throughput screening identifies novel chemical scaffolds targeting Leishmania donovani parasites.World journal of microbiology & biotechnology · 2025Article
- Upregulation of antioxidant genes in antimony-resistant Leishmania tropica clinical isolates.Molecular biology reports · 2025Article
- Genomic characterization of Leishmania (V.) braziliensis associated with antimony therapeutic failure and variable in vitro tolerance to amphotericin B.Scientific reports · 2025Article
- New antifungal strategies and drug development against WHO critical priority fungal pathogens.Frontiers in cellular and infection microbiology · 2025Review
- Harnessing computational methods for uncovering structural insights intoIn silico pharmacology · 2025Article
- Antiprotozoal Natural Products from Endophytic Fungi Associated with Cacao and Coffee.Metabolites · 2024Article
- Sterol 14-alpha demethylase (CYP51) activity in Leishmania donovani is likely dependent upon cytochrome P450 reductase 1.PLoS pathogens · 2024Article
- Arsenic exposure to mouse visceral leishmaniasis model through their drinking water linked to the disease exacerbation via modulation in host protective immunity: a preclinical study.Scientific reports · 2023Article
- Recent Advances in Chemotherapeutics for Leishmaniasis: Importance of the Cellular Biochemistry of the Parasite and Its Molecular Interaction with the Host.Pathogens (Basel, Switzerland) · 2023Review
- Mechanistic insight into the role of mevalonate kinase by a natural fatty acid-mediated killing of Leishmania donovani.Scientific reports · 2022Article
- Amphotericin B resistance in Leishmania mexicana: Alterations to sterol metabolism and oxidative stress response.PLoS neglected tropical diseases · 2022Article
- In silico screening, molecular dynamic simulations, and in vitro activity of selected natural compounds as an inhibitor of Leishmania donovani 3-mercaptopyruvate sulfurtransferase.Parasitology research · 2022Article
- Unraveling of interacting protein network of chaperonin TCP1 gamma subunit of Leishmania donovani.Cell stress & chaperones · 2022Article
- Lipid droplets of protozoan parasites: survival and pathogenicity.Memorias do Instituto Oswaldo Cruz · 2022Article
- Comparative analysis of the transcriptional responses of five Leishmania species to trivalent antimony.Parasites & vectors · 2021Article
- Protein regulation strategies of the mouse spleen in response to Babesia microti infection.Parasites & vectors · 2021Article
- Leishmanicidal Activity of anAntimicrobial agents and chemotherapy · 2020Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leishmania donovani is the causative organism of the neglected human disease known as visceral leishmaniasis which is often fatal, if left untreated. The cysteine biosynthesis pathway of Leishmania may serve as a potential drug target because it is different from human host and regulates downstream components of redox metabolism of the parasites; essential for their survival, pathogenicity and drug resistance. However, despite the apparent dependency of redox metabolism of cysteine biosynthesis pathway, the role of L. donovani cysteine synthase (LdCS) in drug resistance and redox homeostasis has been unexplored. Herein, we report that over-expression of LdCS in Amphotericin B (Amp B) sensitive strain (S1-OE) modulates resistance towards oxidative stress and drug pressure. We observed that antioxidant enzyme activities were up-regulated in S1-OE parasites and these parasites alleviate intracellular reactive oxygen species (ROS) efficiently by maintaining the reduced thiol pool. In contrast to S1-OE parasites, Amp B sensitive strain (S1) showed higher levels of ROS which was positively correlated with the protein carbonylation levels and negatively correlated with cell viability. Moreover, further investigations showed that LdCS over-expression also augments the ROS-primed induction of LdCS-GFP as well as endogenous LdCS and thiol pathway proteins (LdTryS, LdTryR and LdcTXN) in L. donovani parasites; which probably aids in stress tolerance and drug resistance. In addition, the expression of LdCS was found to be up-regulated in Amp B resistant isolates and during infective stationary stages of growth and consistent with these observations, our ex vivo infectivity studies confirmed that LdCS over-expression enhances the infectivity of L. donovani parasites. Our results reveal a novel crosstalk between LdCS and thiol metabolic pathway proteins and demonstrate the crucial role of LdCS in drug resistance and redox homeostasis of Leishmania.
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