ArticleCellular and molecular life sciences : CMLS2016
Comparative genomics of drug resistance in Trypanosoma brucei rhodesiense.
Article in Cellular and molecular life sciences : CMLS, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 25 citations in OpenAlex.
- Drug resistance in animal trypanosomiases: Epidemiology, mechanisms and control strategies.International journal for parasitology. Drugs and drug resistance · 2024Review
- Targeting trypanosomes: how chemogenomics and artificial intelligence can guide drug discovery.Biochemical Society transactions · 2023Review
- Microbiome of rehydrated corn and sorghum grain silages treated with microbial inoculants in different fermentation periods.Scientific reports · 2022Article
- Systematic Review and Meta-Analysis on Human African Trypanocide Resistance.Pathogens (Basel, Switzerland) · 2022Review
- Laboratory Selection of Trypanosomatid Pathogens for Drug Resistance.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Article
- Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites.Microorganisms · 2020Review
- Anti-Trypanosomal Proteasome Inhibitors Cure Hemolymphatic and Meningoencephalic Murine Infection Models of African Trypanosomiasis.Tropical medicine and infectious disease · 2020Article
- The Drugs of Sleeping Sickness: Their Mechanisms of Action and Resistance, and a Brief History.Tropical medicine and infectious disease · 2020Review
- Characterization and phylogenetic analysis of multidrug-resistant protein - encoding genes inVeterinary world · 2019Article
- Evaluation of the Trypanosoma brucei 6-oxopurine salvage pathway as a potential target for drug discovery.PLoS neglected tropical diseases · 2018Article
- 9-(2'-Deoxy-2'-Fluoro-β-d-Arabinofuranosyl) Adenine Is a Potent Antitrypanosomal Adenosine Analogue That Circumvents Transport-Related Drug Resistance.Antimicrobial agents and chemotherapy · 2017Article
- In vitro drug susceptibility of two strains of the wildlife trypanosome, Trypanosoma copemani: A comparison with Trypanosoma cruzi.International journal for parasitology. Drugs and drug resistance · 2017Article
- Exploiting the Achilles' heel of membrane trafficking in trypanosomes.Current opinion in microbiology · 2016Review
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
Trypanosoma brucei rhodesiense is one of the causative agents of human sleeping sickness, a fatal disease that is transmitted by tsetse flies and restricted to Sub-Saharan Africa. Here we investigate two independent lines of T. b. rhodesiense that have been selected with the drugs melarsoprol and pentamidine over the course of 2 years, until they exhibited stable cross-resistance to an unprecedented degree. We apply comparative genomics and transcriptomics to identify the underlying mutations. Only few mutations have become fixed during selection. Three genes were affected by mutations in both lines: the aminopurine transporter AT1, the aquaporin AQP2, and the RNA-binding protein UBP1. The melarsoprol-selected line carried a large deletion including the adenosine transporter gene AT1, whereas the pentamidine-selected line carried a heterozygous point mutation in AT1, G430R, which rendered the transporter non-functional. Both resistant lines had lost AQP2, and both lines carried the same point mutation, R131L, in the RNA-binding motif of UBP1. The finding that concomitant deletion of the known resistance genes AT1 and AQP2 in T. b. brucei failed to phenocopy the high levels of resistance of the T. b. rhodesiense mutants indicated a possible role of UBP1 in melarsoprol-pentamidine cross-resistance. However, homozygous in situ expression of UBP1-Leu(131) in T. b. brucei did not affect the sensitivity to melarsoprol or pentamidine.
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