RNA interference of Trypanosoma brucei cathepsin B and L affects disease progression in a mouse model.

• Published in: PLoS Neglected Tropical Diseases
• Main Authors: Maha-Hamadien Abdulla, Theresa O'Brien, Zachary B Mackey, Mohamed Sajid, Dennis J Grab, James H McKerrow
• Format: Article in Journal/Newspaper
• Language: English
• Published: Public Library of Science (PLoS) 2008
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Public aspects of medicine; RA1-1270; Arctic
• Online Access: https://doi.org/10.1371/journal.pntd.0000298; https://doaj.org/article/f804d8510caf4102ae94c5bdabd1ba55

We investigated the roles played by the cysteine proteases cathepsin B and cathepsin L (brucipain) in the pathogenesis of Trypansoma brucei brucei in both an in vivo mouse model and an in vitro model of the blood-brain barrier. Doxycycline induction of RNAi targeting cathepsin B led to parasite clearance from the bloodstream and prevent a lethal infection in the mice. In contrast, all mice infected with T. brucei containing the uninduced Trypanosoma brucei cathepsin B (TbCatB) RNA construct died by day 13. Induction of RNAi against brucipain did not cure mice from infection; however, 50% of these mice survived 60 days longer than uninduced controls. The ability of T. b. brucei to cross an in vitro model of the human blood-brain barrier was also reduced by brucipain RNAi induction. Taken together, the data suggest that while TbCatB is the more likely target for the development of new chemotherapy, a possible role for brucipain is in facilitating parasite entry into the brain.