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

Maha Hamadien Abdulla, Theresa O'Brien, Zachary B. Mackey, Mohamed Sajid, Dennis J. Grab, James H. McKerrow

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

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.

Original languageEnglish (US)
Title of host publicationPLoS Neglected Tropical Diseases
Volume2
Edition9
DOIs
StatePublished - Aug 2008

ASJC Scopus subject areas

  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • Pharmacology, Toxicology and Pharmaceutics(all)

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