Screening the MMV Pathogen Box reveals the mitochondrial <i>bc</i><sub>1</sub>-complex as a drug target in mature <i>Toxoplasma gondii</i> bradyzoites
The apicomplexan parasite Toxoplasma gondii infects 25–30% of the global human population and can cause life-threatening diseases in immunocompromised patients. The chronically infectious forms of the parasite, bradyzoites, persist within cysts in brain and muscle tissue, and are responsible for its transmission and remission of the disease. Currently available treatment options are very limited…
A recent study screened compounds from the MMV Pathogen Box against Toxoplasma gondii bradyzoites, which are responsible for the chronic stages of the parasite's infection. The researchers utilized a human myotube-based culture model to identify multiple compounds with simultaneous activity against both fast-replicating tachyzoites and the more resistant bradyzoites.
Stable isotope-resolved metabolic profiling on tachyzoites and bradyzoites revealed that the mitochondrial bc 1 -complex is a target of these bradyzocidal compounds and defines their metabolic impacts on both parasite forms. The data suggest that mature bradyzoites rely on mitochondrial ATP production.
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