ArticleCell stress & chaperones2017
Hsp90 inhibitors radicicol and geldanamycin have opposing effects on Leishmania Aha1-dependent proliferation.
Article in Cell stress & chaperones, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
10 citing papers in PubMed, 19 citations in OpenAlex.
- Hsp90 and associates shaping parasite biology.mSphere · 2025Review
- VdAHA1 positively regulate pathogenicity inFrontiers in microbiology · 2025Article
- Impact of Co-chaperones and Posttranslational Modifications Toward Hsp90 Drug Sensitivity.Sub-cellular biochemistry · 2023Article
- Heat Shock Proteins as the Druggable Targets in Leishmaniasis: Promises and Perils.Infection and immunity · 2021Review
- TheGenes · 2020Article
- Article
- Casein kinase 1.2 over expression restores stress resistance to Leishmania donovani HSP23 null mutants.Scientific reports · 2020Article
- Review
- Small Molecule Inhibitors Targeting the Heat Shock Protein System of Human Obligate Protozoan Parasites.International journal of molecular sciences · 2019Review
- Leishmania donovani 90 kD Heat Shock Protein - Impact of Phosphosites on Parasite Fitness, Infectivity and Casein Kinase Affinity.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Hsp90 and its co-chaperones are essential for the medically important parasite Leishmania donovani, facilitating life cycle control and intracellular survival. Activity of Hsp90 is regulated by co-chaperones of the Aha1 and P23 families. In this paper, we studied the expression of L. donovani Aha1 in two life cycle stages, its interaction with Hsp90 and the phenotype of Aha1 null mutants during the insect stage and inside infected macrophages. This study provides a detailed in vitro analysis of the function of Aha1 in Leishmania parasites and the first instance of a reverse genetic analysis of Aha1 in a protozoan parasite. While Aha1 is non-essential under standard growth conditions and at elevated temperature, Aha1 protects against ethanol stress. However, both overexpression and lack of Aha1 affected parasite growth in the presence of the Hsp90 inhibitors radicicol (RAD) and geldanamycin (GA). Under RAD pressure, P23 and Aha1 act in an antagonistic way. By contrast, expression levels of both co-chaperones have similar effects under GA treatment, indicating different inhibition mechanisms by the two compounds. Aha1 is also secreted in virulence-enhancing exosomes. This may explain why the loss of Aha1 reduces the infectivity of L. donovani in ex vivo mouse macrophages, indicating a role during the intracellular mammalian stage.
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Registered trials
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