Nakamura Isabella Bagni, Miguel Danilo Ciccone, Bruscato Andressa, Pereira Mariane Barroso, Campiolo Dimas, de Almeida Antônio Eros, Peloso Eduardo de Figueiredo, Gadelha Fernanda Ramos
Departamento de Bioquímica e Biologia Tecidual, Instituto de Biologia, UNICAMP, Campinas, São Paulo, 13083-862, Brazil.
Departamento de Biologia Animal, Instituto de Biologia, UNICAMP, Campinas, São Paulo, 13083-862, Brazil.
Curr Res Microb Sci. 2022 Feb 9;3:100110. doi: 10.1016/j.crmicr.2022.100110. eCollection 2022.
Chagas disease (CD), caused by , occurs in several countries in Latin America and non-endemic countries. Heterogeneity among population has been the Achilles' heel to find a better treatment for CD. In this study, we characterized the biochemical parameters and mitochondrial bioenergetics of epimastigotes differentiated from eight isolates (I1-I8) obtained from Brazilian CD patients. Molecular analysis of parasites DTUs grouped all of them as TcII. The profile of the growth curves in axenic cultures was distinct among them, except for I1 and I3 and I2 and I4. Doubling times, growth rates, cell body length, and resistance to benznidazole were also significantly different among them. All the isolates were more glucose-dependent than other strains adapted to grow in axenic culture. Mitochondrial bioenergetics analysis showed that each isolate behaved differently regarding oxygen consumption rates in non-permeabilized and in digitonin-permeabilized cells in the presence of a complex II-linked substrate. When complex IV-linked respiratory chain substrate was used to provide electrons to the mitochondrial respiratory chain (MRC), similarity among the isolates was higher. Our findings show that TcII epimastigotes derived from patients' trypomastigotes displayed their own characteristics , highlighting the intra-TcII diversity, especially regarding the functionality of mitochondrial respiratory complexes II and IV. Understanding intraspecific biological features help us to move a step further on our comprehension regarding parasite's survival and adaptability offering clues to improve the development of new therapies for CD.
恰加斯病(CD)由 引起,在拉丁美洲的几个国家以及非流行国家均有发生。人群之间的异质性一直是寻找更好的恰加斯病治疗方法的致命弱点。在本研究中,我们对从巴西恰加斯病患者获得的八个 分离株(I1 - I8)分化而来的前鞭毛体的生化参数和线粒体生物能量学进行了表征。对寄生虫离散型单元(DTUs)的分子分析将它们全部归类为TcII。除了I1和I3以及I2和I4之外,它们在无菌培养中的生长曲线轮廓各不相同。它们之间的倍增时间、生长速率、细胞体长以及对苯硝唑的抗性也存在显著差异。与其他适应在无菌培养中生长的 菌株相比,所有分离株都更依赖葡萄糖。线粒体生物能量学分析表明,在存在复合物II连接底物的情况下,每个分离株在非通透化细胞和洋地黄皂苷通透化细胞中的氧消耗率表现不同。当使用复合物IV连接的呼吸链底物为线粒体呼吸链(MRC)提供电子时,分离株之间的相似性更高。我们的研究结果表明,源自患者锥鞭毛体的TcII前鞭毛体表现出自身特征 ,突出了TcII内部的多样性,特别是关于线粒体呼吸复合物II和IV的功能。了解种内生物学特征有助于我们在理解寄生虫的生存和适应性方面更进一步,为改善恰加斯病新疗法的开发提供线索。