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

作者：Elaadli Haitham; Kim Inyoung; Mackey Zachary B^*

来源：Molecular and Biochemical Parasitology, 2018, 220: 1-4.

DOI：10.1016/j.molbiopara.2017.12.005

• Trypanosoma brucei
• in vivo
• MAPK
• Drug target
• DNA
• replicationReplication
• RNAi

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.

• 出版日期2018-3
• 单位美国弗吉尼亚理工大学(Virginia Tech)