da Costa Rafaella Oliveira, Barreto-Campos Davi, Barbosa-de-Barros Juliana, Frechiani Giovanna, Carvalho-Kelly Luiz Fernando, Carvalho-de-Araújo Ayra Diandra, Meyer-Fernandes José Roberto, Dick Claudia Fernanda
Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro 21590-902, RJ, Brazil.
Graduate Program in Translational Biomedicine/BIOTRANS, Grande Rio University, Duque de Caxias 25071-202, RJ, Brazil.
Pathogens. 2025 Jun 25;14(7):631. doi: 10.3390/pathogens14070631.
is a kinetoplastid parasite and etiological agent of Chagas disease. Given the significant morbidity and mortality rates of this parasitic disease, possible treatment alternatives need to be studied. 3-Bromopyruvate (3-BrPA) is a synthetic analog of pyruvate that was introduced in the early 21st century as an anticancer agent, affecting the proliferation and motility of certain microorganisms. Therefore, this work aims to evaluate the role of 3-BrPA in the energy metabolism, proliferation, and infectivity of , with a primary focus on the mitochondrial state, ATP production, and the key glycolytic pathway enzymes. It was observed that mitochondrial function in 3-BrPA cells was impaired compared to control cells. Accordingly, cells maintained in control conditions have a higher intracellular ATP content than cells maintained with 3-BrPA and higher ecto-phosphatase activity. However, the 3-BrPA reduced ecto-nuclease activity and was capable of hydrolyzing 5'-AMP, ADP, and ATP. When we evaluated two key glycolytic pathway enzymes, glucose kinase (GK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), we observed that 3-BrPA induced higher GAPDH activity but did not alter GK activity. The compensatory energy mechanisms presented in may influence the process of cell metabolism and, consequently, the functional infectious process, suggesting the potential use of 3-BrPA in future clinical applications for Chagas disease.
是一种动基体寄生虫，也是恰加斯病的病原体。鉴于这种寄生虫病的高发病率和死亡率，需要研究可能的治疗替代方案。3-溴丙酮酸（3-BrPA）是丙酮酸的合成类似物，在21世纪初作为抗癌剂被引入，可影响某些微生物的增殖和运动。因此，这项工作旨在评估3-BrPA在的能量代谢、增殖和感染性中的作用，主要关注线粒体状态、ATP生成以及关键糖酵解途径酶。观察到与对照细胞相比，3-BrPA处理的细胞中线粒体功能受损。相应地，处于对照条件下的细胞比用3-BrPA处理的细胞具有更高的细胞内ATP含量和更高的胞外磷酸酶活性。然而，3-BrPA降低了胞外核酸酶活性，并且能够水解5'-AMP、ADP和ATP。当我们评估两种关键糖酵解途径酶，葡萄糖激酶（GK）和甘油醛-3-磷酸脱氢酶（GAPDH）时，我们观察到3-BrPA诱导了更高的GAPDH活性，但没有改变GK活性。中呈现的补偿性能量机制可能会影响细胞代谢过程，进而影响功能性感染过程，这表明3-BrPA在恰加斯病未来临床应用中的潜在用途。
