AUTHOR=Benítez Diego , Ortíz Cecilia , Dibello Estefania , Comini Marcelo A. TITLE=Expanding the applications of a bioluminescent mouse infection model of acute African trypanosomiasis JOURNAL=Frontiers in Chemical Biology VOLUME=3 YEAR=2024 URL=https://www.frontiersin.org/journals/chemical-biology/articles/10.3389/fchbi.2024.1433511 DOI=10.3389/fchbi.2024.1433511 ISSN=2813-530X ABSTRACT=Introduction

In 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.

Methods

The 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.

Results

The 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.

Discussion

The 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.