ArticlePLoS pathogens2017
Aquaglyceroporin-null trypanosomes display glycerol transport defects and respiratory-inhibitor sensitivity.
Article in PLoS pathogens, 2017. 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, 43 citations in OpenAlex.
- Glycosomal Aquaglyceroporin 1 dual role in iron homeostasis and antimony susceptibility in Leishmania amazonensis.PLoS neglected tropical diseases · 2026Article
- Uncovering the Unusual Inhibition Mechanism of a Trypanosome Alternative Oxidase Inhibitor Displaying Broad-Spectrum Activity against African Animal Trypanosomes.Journal of medicinal chemistry · 2025Article
- Antiprotozoal Activity of Plants Used in the Management of Sleeping Sickness in Angola and Bioactivity-Guided Fractionation ofMolecules (Basel, Switzerland) · 2024Article
- Genomic Insight of Leishmania Parasite: In-Depth Review of Drug Resistance Mechanisms and Genetic Mutations.ACS omega · 2024Review
- Tackling Sleeping Sickness: Current and Promising Therapeutics and Treatment Strategies.International journal of molecular sciences · 2023Review
- Application of diffusion weighted multiple boli ASL to a murine model of human African trypanosomiasis.Scientific reports · 2023Article
- Evolutionary Overview of Aquaporin Superfamily.Advances in experimental medicine and biology · 2023Article
- Systematic Review and Meta-Analysis on Human African Trypanocide Resistance.Pathogens (Basel, Switzerland) · 2022Review
- Differences in Transporters Rather than Drug Targets Are the Principal Determinants of the Different Innate Sensitivities ofInternational journal of molecular sciences · 2022Article
- Imidazoline- and Benzamidine-Based Trypanosome Alternative Oxidase Inhibitors: Synthesis and Structure-Activity Relationship Studies.ACS medicinal chemistry letters · 2022Article
- Evolution, function and roles in drug sensitivity of trypanosome aquaglyceroporins.Parasitology · 2021Article
- Glycerol suppresses glucose consumption in trypanosomes through metabolic contest.PLoS biology · 2021Article
- The MRN complex promotes DNA repair by homologous recombination and restrains antigenic variation in African trypanosomes.Nucleic acids research · 2021Article
- Article
- Sterol 14-α-demethylase is vital for mitochondrial functions and stress tolerance in Leishmania major.PLoS pathogens · 2020Article
- Instability of aquaglyceroporin (AQP) 2 contributes to drug resistance in Trypanosoma brucei.PLoS neglected tropical diseases · 2020Article
- Mining Sudanese Medicinal Plants for Antiprotozoal Agents.Frontiers in pharmacology · 2020Article
- An Overview of Drug Resistance in Protozoal Diseases.International journal of molecular sciences · 2019Review
- Chemogenomic Profiling of Antileishmanial Efficacy and Resistance in the Related Kinetoplastid Parasite Trypanosoma brucei.Antimicrobial agents and chemotherapy · 2019Article
- Aquaporin 1 is located on the intestinal basolateral membrane in Toxocara canis and might play a role in drug uptake.Parasites & vectors · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Aquaglyceroporins (AQPs) transport water and glycerol and play important roles in drug-uptake in pathogenic trypanosomatids. For example, AQP2 in the human-infectious African trypanosome, Trypanosoma brucei gambiense, is responsible for melarsoprol and pentamidine-uptake, and melarsoprol treatment-failure has been found to be due to AQP2-defects in these parasites. To further probe the roles of these transporters, we assembled a T. b. brucei strain lacking all three AQP-genes. Triple-null aqp1-2-3 T. b. brucei displayed only a very moderate growth defect in vitro, established infections in mice and recovered effectively from hypotonic-shock. The aqp1-2-3 trypanosomes did, however, display glycerol uptake and efflux defects. They failed to accumulate glycerol or to utilise glycerol as a carbon-source and displayed increased sensitivity to salicylhydroxamic acid (SHAM), octyl gallate or propyl gallate; these inhibitors of trypanosome alternative oxidase (TAO) can increase intracellular glycerol to toxic levels. Notably, disruption of AQP2 alone generated cells with glycerol transport defects. Consistent with these findings, AQP2-defective, melarsoprol-resistant clinical isolates were sensitive to the TAO inhibitors, SHAM, propyl gallate and ascofuranone, relative to melarsoprol-sensitive reference strains. We conclude that African trypanosome AQPs are dispensable for viability and osmoregulation but they make important contributions to drug-uptake, glycerol-transport and respiratory-inhibitor sensitivity. We also discuss how the AQP-dependent inverse sensitivity to melarsoprol and respiratory inhibitors described here might be exploited.
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Registered trials
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