ArticleAntimicrobial agents and chemotherapy2012
Downregulation of mitogen-activated protein kinase 1 of Leishmania donovani field isolates is associated with antimony resistance.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
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- MicroRNA-194 regulates parasitic load and IL-1β-dependent nitric oxide production in the peripheral blood mononuclear cells of dogs with leishmaniasis.PLoS neglected tropical diseases · 2024Article
- Antimony resistance and gene expression inParasitology · 2024Review
- Article
- Distinguishing functions of trypanosomatid protein kinases.Trends in parasitology · 2022Review
- Global distribution of treatment resistance gene markers for leishmaniasis.Journal of clinical laboratory analysis · 2022Review
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- Global genome diversity of theeLife · 2020Article
- Biochemical characterization and chemical validation of Leishmania MAP Kinase-3 as a potential drug target.Scientific reports · 2019Article
- Identifying miltefosine-resistant key genes in protein-protein interactions network and experimental verification in Iranian Leishmania major.Molecular biology reports · 2019Article
- Transcriptional responses of Leishmania (Leishmania) amazonensis in the presence of trivalent sodium stibogluconate.Parasites & vectors · 2019Article
- Genomic insights into virulence mechanisms of Leishmania donovani: evidence from an atypical strain.BMC genomics · 2018Article
- Emerging therapeutic targets for treatment of leishmaniasis.Expert opinion on therapeutic targets · 2018Review
- Evaluating drug resistance in visceral leishmaniasis: the challenges.Parasitology · 2018Review
- MAPK1 of Leishmania donovani interacts and phosphorylates HSP70 and HSP90 subunits of foldosome complex.Scientific reports · 2017Article
- Enzyme Activity Assays for Protein Kinases: Strategies to Identify Active Substrates.Current drug discovery technologies · 2016Review
- Over-Expression of Cysteine Leucine Rich Protein Is Related to SAG Resistance in Clinical Isolates of Leishmania donovani.PLoS neglected tropical diseases · 2015Article
- MAPK1 of Leishmania donovani modulates antimony susceptibility by downregulating P-glycoprotein efflux pumps.Antimicrobial agents and chemotherapy · 2015Article
- Drug resistance analysis by next generation sequencing in Leishmania.International journal for parasitology. Drugs and drug resistance · 2015Review
- A Multiplatform Metabolomic Approach to the Basis of Antimonial Action and Resistance in Leishmania infantum.PloS one · 2015Article
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Emergence of resistance to pentavalent antimonials has become a severe obstacle in the treatment of visceral leishmaniasis (VL) on the Indian subcontinent. The mechanisms operating in laboratory-generated strains are somewhat known, but the determinants of clinical antimony resistance are not well understood. By utilizing a DNA microarray expression profiling approach, we identified a gene encoding mitogen-activated protein kinase 1 (MAPK1) for the kinetoplast protozoan Leishmania donovani (LdMAPK1) that was consistently downregulated in antimony-resistant field isolates. The expression level of the gene was validated by real-time PCR. Furthermore, decreased expression of LdMAPK1 was also confirmed at the protein level in resistant isolates. Primary structure analysis of LdMAPK1 revealed the presence of all of the characteristic features of MAPK1. When expressed in Escherichia coli, the recombinant enzyme showed kinase activity with myelin basic protein as the substrate and was inhibited by staurosporine. Interestingly, overexpression of this gene in a drug-sensitive laboratory strain and a resistant field isolate resulted in increased the sensitivity of the transfectants to potassium antimony tartrate, suggesting that it has a role in antimony resistance. Our results demonstrate that downregulation of LdMAPK1 may be in part correlated with antimony drug resistance in Indian VL isolates.
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