ArticleProceedings of the National Academy of Sciences of the United States of America2012
Aquaglyceroporin 2 controls susceptibility to melarsoprol and pentamidine in African trypanosomes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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Who cites it
87 citing papers in PubMed, 159 citations in OpenAlex.
- Canalesolide A, a Structurally Unique Polyhydroxy Macrolide from the Marine Cyanobacterium Okeania sp. with Potent Antitrypanosomal Activity.Journal of the American Chemical Society · 2026Article
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- Pathogenic Significance of Trypanosomatids: Progress in Drug Resistance, Control Strategies, and Artificial Intelligence.Interdisciplinary perspectives on infectious diseases · 2026Review
- Molecular mechanisms underlying drug resistance in protozoan parasites: emerging mechanisms and therapeutic perspectives.Frontiers in parasitology · 2026Review
- A CRISPR-based diagnostic tool to survey drug resistance in human African trypanosomiasis.Antimicrobial agents and chemotherapy · 2025Article
- Uncovering the Unusual Inhibition Mechanism of a Trypanosome Alternative Oxidase Inhibitor Displaying Broad-Spectrum Activity against African Animal Trypanosomes.Journal of medicinal chemistry · 2025Article
- NewRSC medicinal chemistry · 2025Article
- Transforming the chemotherapy of human African trypanosomiasis.Clinical microbiology reviews · 2025Review
- One Health policy for combatting African trypanocide resistance.One health (Amsterdam, Netherlands) · 2024Article
- Post-transcriptional reprogramming by thousands of mRNA untranslated regions in trypanosomes.Nature communications · 2024Article
- Drug resistance in animal trypanosomiases: Epidemiology, mechanisms and control strategies.International journal for parasitology. Drugs and drug resistance · 2024Review
- Structural insights into drug transport by an aquaglyceroporin.Nature communications · 2024Article
- High-Throughput Phenotypic Screening and Machine Learning Methods Enabled the Selection of Broad-Spectrum Low-Toxicity Antitrypanosomatidic Agents.Journal of medicinal chemistry · 2023Article
- Bis-6-amidino-benzothiazole Derivative that Cures Experimental Stage 1 African Trypanosomiasis with a Single Dose.Journal of medicinal chemistry · 2023Article
- 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
- Arsenic in medicine: past, present and future.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2023Review
- Targeted Protein Degradation for Infectious Diseases: from Basic Biology to Drug Discovery.ACS bio & med chem Au · 2023Review
- TUSK: a ubiquitin hydrolase complex modulating surface protein abundance in trypanosomes.Frontiers in parasitology · 2023Article
- Down the membrane hole: Ion channels in protozoan parasites.PLoS pathogens · 2022Review
27 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
African trypanosomes cause sleeping sickness in humans, a disease that is typically fatal without chemotherapy. Unfortunately, drug resistance is common and melarsoprol-resistant trypanosomes often display cross-resistance to pentamidine. Although melarsoprol/pentamidine cross-resistance (MPXR) has been an area of intense interest for several decades, our understanding of the underlying mechanisms remains incomplete. Recently, a locus encoding two closely related aquaglyceroporins, AQP2 and AQP3, was linked to MPXR in a high-throughput loss-of-function screen. Here, we show that AQP2 has an unconventional "selectivity filter." AQP2-specific gene knockout generated MPXR trypanosomes but did not affect resistance to a lipophilic arsenical, whereas recombinant AQP2 reversed MPXR in cells lacking native AQP2 and AQP3. AQP2 was also shown to be disrupted in a laboratory-selected MPXR strain. Both AQP2 and AQP3 gained access to the surface plasma membrane in insect life-cycle-stage trypanosomes but, remarkably, AQP2 was specifically restricted to the flagellar pocket in the bloodstream stage. We conclude that the unconventional aquaglyceroporin, AQP2, renders cells sensitive to both melarsoprol and pentamidine and that loss of AQP2 function could explain cases of innate and acquired MPXR.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.