BjussuLAAO-II, an l-amino acid oxidase from Bothrops jararacussu snake venom, impairs Toxoplasma gondii infection in human trophoblast cells and villous explants from the third trimester of pregnancy

Microbes Infect. 2023 Jul-Aug;25(6):105123. doi: 10.1016/j.micinf.2023.105123. Epub 2023 Mar 2.

Abstract

One-third of the world's population is estimated to be affected by toxoplasmosis. Pregnancy-related Toxoplasma gondii infection can cause vertical transmission, infect the fetus, and cause miscarriage, stillbirth, and fetal death. The current study showed that both human trophoblast cells (BeWo lineage) and human explant villous were resistant to T. gondii infection after incubation with BjussuLAAO-II, an l-amino acid oxidase isolated from Bothrops jararacussu. Almost 90% of the parasite's ability to proliferate in BeWo cells was decreased by the toxin at 1.56 μg/mL and showed an irreversible anti-T. gondii effect. Also, BjussuLAAO-II impaired the key events of adhesion and invasion of T. gondii tachyzoites in BeWo cells. BjussuLAAO-II antiparasitic properties were associated with the intracellular production of reactive oxygen species and hydrogen peroxide, since the presence of catalase restored the parasite's growth and invasion. In addition, T. gondii growth in human villous explants was decreased to approximately 51% by the toxin treatment at 12.5 μg/mL. Furthermore, BjussuLAAO-II treatment altered IL-6, IL-8, IL-10 and MIF cytokines levels, assuming a pro-inflammatory profile in the control of T. gondii infection. This study contributes to the potential use of a snake venom l-amino acid oxidase for the development of agents against congenital toxoplasmosis and the discovery of new targets in parasites and host cells.

Keywords: Congenital toxoplasmosis; Snake venom; Toxoplasma gondii; Trophoblast cells; Villous explants; l-amino acid oxidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bothrops*
  • Female
  • Humans
  • L-Amino Acid Oxidase / pharmacology
  • Pregnancy
  • Pregnancy Trimester, Third
  • Snake Venoms
  • Toxoplasma*
  • Toxoplasmosis* / parasitology
  • Trophoblasts / parasitology
  • Venomous Snakes

Substances

  • L-Amino Acid Oxidase
  • Snake Venoms

Supplementary concepts

  • Bothrops jararacussu