Targeting Dihydrofolate Reductase-Thymidylate Synthase in African Trypanosomes
Author Information
Author(s): Sienkiewicz, Natasha, Jarosławski, Szymon, Wyllie, Susan, Fairlamb, Alan H
Primary Institution: University of Dundee
Hypothesis
Is dihydrofolate reductase-thymidylate synthase essential for the survival of African trypanosomes?
Conclusion
Dihydrofolate reductase-thymidylate synthase is essential for the survival of African trypanosomes and represents a promising drug target.
Supporting Evidence
- Knockout mutants of the enzyme were unable to infect mice, indicating its essential role.
- Restoration of virulence was possible by transfecting the knockout mutants with the enzyme from T. brucei.
- Drugs targeting the enzyme were found to be significantly more effective in low-folate conditions.
Takeaway
This study shows that a specific enzyme is crucial for the survival of a parasite that causes sleeping sickness, which could help in developing new treatments.
Methodology
The study involved creating knockout mutants of the enzyme in trypanosomes and testing their growth and virulence in vitro and in vivo.
Limitations
The study primarily focuses on specific knockout lines and may not account for all genetic variations in natural populations of the parasite.
Digital Object Identifier (DOI)
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