Exploring the energetic metabolism of Toxoplasma gondii: evaluating the impact of atovaquone

Abstract

Toxoplasmosis is a disease with a wide host range and is considered a public health problem that affects approximately one third of the world's population. In adults, it ranges from benign to ocular and neurological infections and may be more severe in immunocompromised individuals and when transmitted congenitally. The toxoplasmosis treatment protocol, which has remained the same since the 1990s, is considered complex as the drugs currently used do not eliminate the parasite. Therefore, this study aims to evaluate the in vitro metabolic impact of atovaquone on acute (RH) and cystogenic (ME49) strains of Toxoplasma gondii. The strains were cultured and exposed to different concentrations of atovaquone for 7 days. Glycolysis, lactic fermentation, and tricarboxylic acid cycle (TCA) metabolites were quantified by high-performance liquid chromatography (HPLC) and spectrophotometry. The replication rate was drastically impaired in both strains when exposed to 100 nM of atovaquone. After exposure to the drug, glucose was significantly reduced in both strains, being below detection levels for the longest time evaluated, and phosphoenolpyruvate (PEP) behaved similarly. Lactic fermentation was impaired in the RH strain, where lactate was found to be reduced in relation to the control group. The TCA cycle was partially affected in both strains due to a significant decrease in oxaloacetate and α-ketoglutarate concentrations throughout the experimental period. The impact of atovaquone on the energy metabolism of T. gondii may have contributed to the decrease in the parasite's replication rate, demonstrating a promising alternative option for the treatment of toxoplasmosis.