ArticleAntimicrobial agents and chemotherapy2008
Roles of trypanothione S-transferase and tryparedoxin peroxidase in resistance to antimonials.
Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 78 citations in OpenAlex.
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- The carbonic anhydrase enzymes as new targets for the management of neglected tropical diseases.Archiv der Pharmazie · 2025Review
- Deciphering Host-Parasite Interplay inACS infectious diseases · 2024Article
- Antimony resistance and gene expression inParasitology · 2024Review
- Label-Free Mass Spectrometry Proteomics Reveals Different Pathways Modulated in THP-1 Cells Infected with Therapeutic Failure and Drug ResistanceACS infectious diseases · 2023Article
- Fatty Acid Composition and Metabolism inInternational journal of molecular sciences · 2023Review
- Global distribution of treatment resistance gene markers for leishmaniasis.Journal of clinical laboratory analysis · 2022Review
- Polyamine Metabolism inMedical sciences (Basel, Switzerland) · 2022Review
- Antioxidant defence system as a rational target for Chagas disease and Leishmaniasis chemotherapy.Memorias do Instituto Oswaldo Cruz · 2022Review
- Exploring direct and indirect targets of current antileishmanial drugs using a novel thermal proteomics profiling approach.Frontiers in cellular and infection microbiology · 2022Article
- Chalcones identify cTXNPx as a potential antileishmanial drug target.PLoS neglected tropical diseases · 2021Article
- Serine proteases profiles of Leishmania (Viannia) braziliensis clinical isolates with distinct susceptibilities to antimony.Scientific reports · 2021Article
- Perspectives From Systems Biology to Improve Knowledge ofFrontiers in cellular and infection microbiology · 2021Article
- Polyamines in protozoan pathogens.The Journal of biological chemistry · 2018Review
- Discovery and Genetic Validation of Chemotherapeutic Targets for Chagas' Disease.Frontiers in cellular and infection microbiology · 2018Review
- Drug resistance and treatment failure in leishmaniasis: A 21st century challenge.PLoS neglected tropical diseases · 2017Review
- 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
- Drug resistance in eukaryotic microorganisms.Nature microbiology · 2016Review
- Studies of the Effectiveness of Bisphosphonate and Vanadium-Bisphosphonate Compounds In Vitro against Axenic Leishmania tarentolae.Oxidative medicine and cellular longevity · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The clinical value of antimonial drugs, the mainstay therapy for leishmaniasis, is now threatened by the emergence of acquired drug resistance, and a comprehensive understanding of the underlying mechanisms is required. Using the model organism Leishmania tarentolae, we have examined the role of trypanothione S-transferase (TST) in trivalent antimony [Sb(III)] resistance. TST has S-transferase activity with substrates such as chlorodinitrobenzene as well as peroxidase activity with alkyl and aryl hydroperoxides but not with hydrogen peroxide. Although S-transferase activity and TST protein levels were unchanged in Sb(III)-sensitive and -resistant lines, rates of metabolism of hydrogen peroxide, t-butyl hydroperoxide, and cumene hydroperoxide were significantly increased. Elevated peroxidase activities were shown to be both trypanothione and tryparedoxin dependent and were associated with the overexpression of classical tryparedoxin peroxidase (TryP) in the cytosol of L. tarentolae. The role of TryP in Sb(III) resistance was verified by overexpression of the recombinant Leishmania major protein in Sb(III)-sensitive promastigotes. An approximate twofold increase in the level of TryP activity in this transgenic cell line was accompanied by a significant decrease in sensitivity to Sb(III) (twofold; P < 0.001). Overexpression of an enzymatically inactive TryP failed to result in Sb(III) resistance. This indicates that TryP-dependent resistance is not due to sequestration of Sb(III) and suggests that enhanced antioxidant defenses may well be a key feature of mechanisms of clinical resistance to antimonial drugs.
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