MjTX-II, a Lys49-PLA2 from Bothrops moojeni snake venom, restricts Toxoplasma gondii infection via ROS and VEGF regulation

Abstract

Owing to the lack of efficient therapy and emerging resistance strains, toxoplasmosis affects about one-third of the world's population. Also, pregnancy-related infection can cause vertical transmission and result in fetal death. Despite the global efforts to combat Toxoplasma gondii infection, conventional therapies have been associated with serious side effects. Therefore, it is relevant to search for effective and less-toxic treatments of toxoplasmosis. In this scenario, snake venoms emerged as a promising source of therapeutic molecules due to their wide variety of biological effects. The present study investigated the anti-T. gondii effects of MjTX-II, a Lys49-PLA₂ isolated from Bothrops moojeni, in trophoblast cells and villous explants from the third trimester of pregnancy. We found that non-cytotoxic doses of MjTX-II impaired parasite invasion and intracellular growth in BeWo cells. Also, MjTX–II–pre-treated T. gondii tachyzoites exhibited irregular rough surfaces, papules, and dimples, suggesting a possible action directly on the parasites. Moreover, MjTX-II was able to modulate the host environment by increasing ROS and cytokine levels involved in the control of infection. In addition, we observed that MjTX-II decreased VEGF levels and the addition of rVEGF increased T. gondii growth in BeWo cells. Through molecular docking simulations, we verified that MjTX-II is able to bind VEGFR2 and ICAM-1 receptors associated with parasite proliferation and dissemination. This work contributes to the discovery of therapeutic targets against T. gondii infection and for the development of effective and low-toxic antiparasitic molecules against congenital toxoplasmosis.