de Melo Fernandes Thales Alves, Teixeira Samuel Cota, Costa Tássia Rafaela, Rosini Alessandra Monteiro, de Souza Guilherme, Polloni Lorena, Barbosa Bellisa de Freitas, Silva Marcelo José Barbosa, Ferro Eloisa Amália Vieira, Ávila Veridiana de Melo Rodrigues
Laboratory of Biochemistry and Animal Toxins, Institute of Biotechnology, Federal University of Uberlândia, Campus Umuarama, St. Acre s/n, 38402-902, Uberlândia, MG, Brazil.
Laboratory of Immunophysiology of Reproduction, Institute of Biomedical Science, Federal University of Uberlândia, Campus Umuarama, Av. Para, 1720, 38400-239, Uberlândia, MG, Brazil.
Microbes Infect. 2023 Jul-Aug;25(6):105123. doi: 10.1016/j.micinf.2023.105123. Epub 2023 Mar 2.
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.
据估计,全球三分之一的人口受到弓形虫病的影响。与妊娠相关的弓形虫感染可导致垂直传播,感染胎儿,并导致流产、死产和胎儿死亡。目前的研究表明,在与从巴西矛头蝮蛇分离的L-氨基酸氧化酶BjussuLAAO-II孵育后,人滋养层细胞(BeWo谱系)和人绒毛外植体对弓形虫感染具有抗性。在1.56μg/mL的毒素作用下,几乎90%的寄生虫在BeWo细胞中的增殖能力下降,并显示出不可逆的抗弓形虫作用。此外,BjussuLAAO-II损害了弓形虫速殖子在BeWo细胞中粘附和侵袭的关键事件。BjussuLAAO-II的抗寄生虫特性与细胞内活性氧和过氧化氢的产生有关,因为过氧化氢酶的存在恢复了寄生虫的生长和侵袭。此外,在12.5μg/mL的毒素处理下,人绒毛外植体中弓形虫的生长降低至约51%。此外,BjussuLAAO-II处理改变了IL-6、IL-8、IL-10和MIF细胞因子水平,在控制弓形虫感染方面呈现出促炎特征。这项研究有助于蛇毒L-氨基酸氧化酶在开发抗先天性弓形虫病药物以及发现寄生虫和宿主细胞新靶点方面的潜在应用。