Depletion of the extracellular-signal regulated kinase 8 homolog in Trypanosoma brucei in vivo reduces its virulence in a mouse target validation study

[Display omitted] •Depletion of TbERK8 in Trypanosoma brucei reduces its virulence in mouse infection.•TbERK8 is linked to processes involved in T. brucei genomic maintenance.•Validation of TbERK8 as an attractive target for drug discovery. Trypanosoma brucei sub-species are vector borne kinetoplastid parasites that cause the potentially lethal disease Human African trypanosomiasis. The target-based therapy for curing this parasitic disease relies on one drug, Eflornithine. The roles of mitogen-activated protein kinases in regulating key cellular processes in eukaryotic cells such as proliferation, stress response and differentiation plus their druggability make them attractive targets for therapeutic exploitation. The extracellular-regulated kinase 8 homolog in T. brucei (TbERK8) is a MAPK that is required for the parasite to proliferate normally in culture. We examined the importance of TbERK8 for permitting T. brucei to thrive in mice. Here we show that depleting TbERK8 in vivo negatively affected the virulence of T. brucei reducing its ability to progress to lethal infections or cause significant pathology in mice, which validates it as an attractive target.