Expanding the applications of a bioluminescent mouse infection model of acute African trypanosomiasis

Abstract

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IntroductionIn vivo imaging technology based on bioluminescence has contributed to the study of different pathophysiological conditions involving inherited or transmissible diseases. Here, we aimed to establish a bioluminescent model of acute African trypanosomiasis for a manifold of applications. African trypanosomiasis is a neglected tropical disease that threatens human and animal health, mainly in sub-Saharan countries, for which new chemotherapies are needed.MethodsThe model relies on a hypervirulent bloodstream form of Trypanosoma brucei brucei, which constitutively expresses red-shifted luciferase, and an infection-susceptible murine host, Balb/cJ mouse. In vivo and ex vivo imaging techniques were applied to obtain a spatial, temporal, and quantitative (parasite load) resolution of the infection process and to refine the animal endpoint criterion.ResultsThe model proved suitable for validating the essentiality of the parasite enzyme glucose 6-phosphate dehydrogenase by reverse genetics (tetracycline-inducible double-strand RNA interference). The efficacy of drugs (monotherapy or a new combination) for the treatment of the acute stage of the disease was successfully explored by in vivo imaging.DiscussionThe new bioluminescent model developed here may represent a valuable tool for speeding up the drug discovery process and the investigation of host-pathogen interactions in the acute stage of African sleeping sickness.

Keywords

• bioluminescence
• drug efficacy
• genetic validation
• glucose 6-phosphate dehydrogenase
• dsRNAi
• red-shifted luciferase