ArticleAntimicrobial agents and chemotherapy2006
Resistance of Leishmania donovani to sodium stibogluconate is related to the expression of host and parasite gamma-glutamylcysteine synthetase.
Article in Antimicrobial agents and chemotherapy, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 50 citations in OpenAlex.
- Antimony resistance and gene expression inParasitology · 2024Review
- Global distribution of treatment resistance gene markers for leishmaniasis.Journal of clinical laboratory analysis · 2022Review
- Transcriptomic Analysis in Human Macrophages Infected with Therapeutic Failure Clinical Isolates ofACS infectious diseases · 2022Article
- Treatment failure to sodium stibogluconate in cutaneous leishmaniasis: A challenge to infection control and disease elimination.PloS one · 2021Article
- Profiling gene expression of antimony response genes in Leishmania (Viannia) panamensis and infected macrophages and its relationship with drug susceptibility.Acta tropica · 2017Article
- Increased miltefosine tolerance in clinical isolates of Leishmania donovani is associated with reduced drug accumulation, increased infectivity and resistance to oxidative stress.PLoS neglected tropical diseases · 2017Article
- The leishmanicidal activity of oleuropein is selectively regulated through inflammation- and oxidative stress-related genes.Parasites & vectors · 2016Article
- Decreased antimony uptake and overexpression of genes of thiol metabolism are associated with drug resistance in a canine isolate of Leishmania infantum.International journal for parasitology. Drugs and drug resistance · 2016Article
- Cross-resistance of Leishmania infantum isolates to nitric oxide from patients refractory to antimony treatment, and greater tolerance to antileishmanial responses by macrophages.Parasitology research · 2016Article
- Stage-dependent expression and up-regulation of trypanothione synthetase in amphotericin B resistant Leishmania donovani.PloS one · 2014Article
- Leishmania antimony resistance: what we know what we can learn from the field.Parasitology research · 2011Review
- Gene expression profiling and molecular characterization of antimony resistance in Leishmania amazonensis.PLoS neglected tropical diseases · 2011Article
- Antimony resistance in leishmania, focusing on experimental research.Journal of tropical medicine · 2011Article
- Use of antimony in the treatment of leishmaniasis: current status and future directions.Molecular biology international · 2011Article
- RETRACTED: Leishmania donovani isolates with antimony-resistant but not -sensitive phenotype inhibit sodium antimony gluconate-induced dendritic cell activation.PLoS pathogens · 2010Article
- Frequency of drug resistance gene amplification in clinical leishmania strains.International journal of microbiology · 2010Article
- Drug resistance in visceral leishmaniasis.Journal of biomedicine & biotechnology · 2010Review
- Modulation of gene expression in human macrophages treated with the anti-leishmania pentavalent antimonial drug sodium stibogluconate.Antimicrobial agents and chemotherapy · 2008Article
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7 authors at 2 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
Abstract
Sequencing studies showed that the gamma-glutamylcysteine synthetase (gamma-GCS) heavy chain genes from sodium stibogluconate (SSG)-resistant (SSG-R) and SSG-susceptible (SSG-S) Leishmania donovani strains were identical, indicating that SSG resistance was related to quantitative differences in gamma-GCS expression rather than gene interstrain polymorphisms. In vitro infection of murine macrophages with the SSG-R strain, but not the SSG-S strain, down regulated expression of host gamma-GCS, which would result in a reduction in intramacrophage glutathione (GSH) levels and promote an oxidative intramacrophage environment. This would inhibit, or minimize, the reduction of SSG pentavalent antimony to its more toxic trivalent form. Macrophage studies showed that the SSG-R strain expressed higher levels of gamma-GCS compared to the SSG-S strain, which would result in higher GSH levels, giving increased protection against oxidative stress and facilitating SSG efflux. However a similar differential effect on host and parasite gamma-GCS expression was not obtained when using tissues from infected mice. In this case gamma-GCS expression was organ and strain dependent for both the host and the parasite, indicating that environmental conditions have a profound effect on gamma-GCS expression. Consistent with the proposed mechanism from in vitro studies, increasing tissue GSH levels in the presence of SSG by cotreatment of L. donovani-infected mice with SSG solution and GSH incorporated into nonionic surfactant vesicles was more effective in reducing liver, spleen, and bone marrow parasite burdens than monotherapy with SSG. Together, these results indicate that SSG resistance is associated with manipulation of both host and parasite GSH levels by L. donovani.
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