ArticleInternational journal for parasitology. Drugs and drug resistance2013
Functional expression of TcoAT1 reveals it to be a P1-type nucleoside transporter with no capacity for diminazene uptake.
Article in International journal for parasitology. Drugs and drug resistance, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 64 citations in OpenAlex.
- Resistance to trypanocidal drugs in cattle populations of Zambezia Province, Mozambique.Parasitology research · 2018Trial
- A cell surface transporter mediates phenanthridine resistance in African trypanosomes.npj antimicrobials and resistance · 2026Article
- Interventions for Neglected Diseases Caused by Kinetoplastid Parasites: A One Health Approach to Drug Discovery, Development, and Deployment.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Drug resistance in animal trypanosomiases: Epidemiology, mechanisms and control strategies.International journal for parasitology. Drugs and drug resistance · 2024Review
- Trypanosoma Congolense Resistant to Trypanocidal Drugs Homidium and Diminazene and their Molecular Characterization in Lambwe, Kenya.Acta parasitologica · 2023Article
- Cloning and Characterization ofInternational journal of molecular sciences · 2023Article
- Nucleoside Transport and Nucleobase Uptake Null Mutants inInternational journal of molecular sciences · 2022Article
- Differences in Transporters Rather than Drug Targets Are the Principal Determinants of the Different Innate Sensitivities ofInternational journal of molecular sciences · 2022Article
- The Antiprotozoal Activity of Papua New Guinea Propolis and Its Triterpenes.Molecules (Basel, Switzerland) · 2022Article
- AInternational journal of molecular sciences · 2022Article
- An Update on African Trypanocide Pharmaceutics and Resistance.Frontiers in veterinary science · 2022Review
- The COMBAT project: controlling and progressively minimizing the burden of vector-borne animal trypanosomosis in Africa.Open research Europe · 2022Article
- Comprehensive characterization of purine and pyrimidine transport activities in Trichomonas vaginalis and functional cloning of a trichomonad nucleoside transporter.Molecular microbiology · 2021Article
- Article
- Tackling protozoan parasites of cattle in sub-Saharan Africa.PLoS pathogens · 2021Article
- Divergent metabolism between Trypanosoma congolense and Trypanosoma brucei results in differential sensitivity to metabolic inhibition.PLoS pathogens · 2021Article
- Molecular identification of diminazene aceturate resistant trypanosomes in tsetse flies from Yoko in the Centre region of Cameroon and its epidemiological implications.Parasite epidemiology and control · 2020Article
- The Drugs of Sleeping Sickness: Their Mechanisms of Action and Resistance, and a Brief History.Tropical medicine and infectious disease · 2020Review
- Article
- Functional and genetic evidence that nucleoside transport is highly conserved in Leishmania species: Implications for pyrimidine-based chemotherapy.International journal for parasitology. Drugs and drug resistance · 2017Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
It has long been established that the Trypanosoma brucei TbAT1/P2 aminopurine transporter is involved in the uptake of diamidine and arsenical drugs including pentamidine, diminazene aceturate and melarsoprol. Accordingly, it was proposed that the closest Trypanosoma congolense paralogue, TcoAT1, might perform the same function in this parasite, and an apparent correlation between a Single Nucleotide Polymorphism (SNP) in that gene and diminazene tolerance was reported for the strains examined. Here, we report the functional cloning and expression of TcoAT1 and show that in fact it is the syntenic homologue of another T. brucei gene of the same Equilibrative Nucleoside Transporter (ENT) family: TbNT10. The T. congolense genome does not seem to contain a syntenic equivalent to TbAT1. Two TcoAT1 alleles, differentiated by three independent SNPs, were expressed in the T. brucei clone B48, a TbAT1-null strain that further lacks the High Affinity Pentamidine Transporter (HAPT1); TbAT1 was also expressed as a control. The TbAT1 and TcoAT1 transporters were functional and increased sensitivity to cytotoxic nucleoside analogues. However, only TbAT1 increased sensitivity to diamidines and to cymelarsan. Uptake of [(3)H]-diminazene was detectable only in the B48 cells expressing TbAT1 but not TcoAT1, whereas uptake of [(3)H]-inosine was increased by both TcoAT1 alleles but not by TbAT1. Uptake of [(3)H]-adenosine was increased by all three ENT genes. We conclude that TcoAT1 is a P1-type purine nucleoside transporter and the syntenic equivalent to the previously characterised TbNT10; it does not mediate diminazene uptake and is therefore unlikely to play a role in diminazene resistance in T. congolense.
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