Article
4E interacting protein as a potential novel drug target for nucleoside analogues in Trypanosoma brucei
Registro en:
MABILLE, Dorien et al. 4E interacting protein as a potential novel drug target for nucleoside analogues in Trypanosoma brucei. Microorganisms, v. 9, n. 4, p. 1-16, 13 Apr. 2021.
2076-2607
10.3390/microorganisms9040826
2076-2607
Autor
Mabille, Dorien
Santos, Camila Cardoso
Hendrickx, Rik
Claes, Mathieu
Takac, Peter
Clayton, Christine
Hendrickx, Sarah
Hulpia, Fabian
Maes, Louis
Van Calenbergh, Serge
Caljon, Guy
Resumen
Human African trypanosomiasis is a neglected parasitic disease for which the current treatment options are quite limited. Trypanosomes are not able to synthesize purines de novo and thus solely depend on purine salvage from the host environment. This characteristic makes players of the purine salvage pathway putative drug targets. The activity of known nucleoside analogues such as tubercidin and cordycepin led to the development of a series of C7-substituted nucleoside analogues. Here, we use RNA interference (RNAi) libraries to gain insight into the mode-of-action of these novel nucleoside analogues. Whole-genome RNAi screening revealed the involvement of adenosine kinase and 4E interacting protein into the mode-of-action of certain antitrypanosomal nucleoside analogues. Using RNAi lines and gene-deficient parasites, 4E interacting protein was found to be essential for parasite growth and infectivity in the vertebrate host. The essential nature of this gene product and involvement in the activity of certain nucleoside analogues indicates that it represents a potential novel drug target.