Trypanosoma congolense is the main parasite causing Animal African Trypanosomiasis (AAT) with dev-astating consequences to livestock health and economics in sub-Saharan Africa. Isometamidium Chlo-ride (ISM) is one of the principle drugs used against the disease. While resistance to ISM has become problematic, its mechanisms are yet to be discovered. Transporter proteins are of utmost interest in drug development as they allow the drug to enter the cell and/or its target organelle as well as its ef-flux to avoid damage. When comparing the genome of ISM-sensitive and resistant strains, we have already identified a series of non-synonymous point mutations in genes coding for different transport-ers and transmembrane proteins, suggesting that drug transport may be the underlying basis for the acquisition of ISM resistance in T. congolense. Here, we want to develop novel genetic tools for trans-formation of bloodstream stage T. congolense, allowing to demonstrate the involvement of trans-porters in ISM uptake and resistance. As the actual toolkit panel available for this parasite is very lim-ited, the development of interference RNA, CRISPR and fluorescent tagging techniques is a keystone for advanced studies on the molecular basis of drug resistance. These novel tools will be used in a fu-ture full-scale project that aims to investigate the possible impact of gene mutations on the up-take/efflux of ISM and their functional association with the drug resistance phenotype.
|Effective start/end date||1/10/18 → 31/12/20|
- Institute of Tropical Medicine, Antwerp: €47,915.00