Molecular Parasitology Unit, Medical Technology Department, University of Antofagasta, Antofagasta, Chile.
Laboratory of Gap Junction Proteins and Parasitic Disease, Instituto Antofagasta, Universidad de Antofagasta, Antofagasta, Chile.
Virulence. 2022 Dec;13(1):1827-1848. doi: 10.1080/21505594.2022.2132776.
The molecular repertoire of effects its virulence and impacts the clinical course of the resulting Chagas disease. This study aimed to determine the mechanism underlying the pathogenicity of . Two cell lines (C8C3 and C8C3), obtained from the clone H510 C8C3 and exhibiting different virulence phenotypes, were used to evaluate the parasite's infectivity in mice. The organ parasite load was analysed by qPCR. The proteomes of both cell lines were compared using nLC-MS/MS. Cruzipain (Czp), complement regulatory protein (CRP), trans-sialidase (TS), Tc-85, and sialylated epitope expression levels were evaluated by immunoblotting. High-virulence C8C3 was highly infectious in mice and demonstrated three to five times higher infectivity in mouse myocardial cells than low-virulence C8C3. qPCR revealed higher parasite loads in organs of acute as well as chronically C8C3-infected mice than in those of C8C3-infected mice. Comparative quantitative proteomics revealed that 390 of 1547 identified proteins were differentially regulated in C8C3 with respect to C8C3. Amongst these, 174 proteins were upregulated in C8C3 and 216 were downregulated in C8C3. The upregulated proteins in C8C3 were associated with the tricarboxylic acid cycle, ribosomal proteins, and redoxins. Higher levels of Czp, CRP, TS, Tc-85, and sialylated epitopes were expressed in C8C3 than in C8C3. Thus, virulence may be related to virulence factor expression as well as upregulation of bioenergetic and biosynthetic pathways proteins.
效应的分子谱影响其毒力，并影响由此产生的克氏锥虫病的临床过程。本研究旨在确定 致病的机制。使用两种 细胞系（C8C3 和 C8C3），它们来自克隆 H510 C8C3，表现出不同的毒力表型，用于评估寄生虫在小鼠中的感染性。通过 qPCR 分析器官寄生虫负荷。使用 nLC-MS/MS 比较两种 细胞系的蛋白质组。通过免疫印迹评估 cruzipain (Czp)、补体调节蛋白 (CRP)、转涎酶 (TS)、Tc-85 和唾液酸化表位的表达水平。高毒力 C8C3 在小鼠中具有高度传染性，在感染小鼠心肌细胞的感染性比低毒力 C8C3 高 3 到 5 倍。qPCR 显示急性和慢性 C8C3 感染小鼠的器官寄生虫负荷高于 C8C3 感染小鼠。比较定量蛋白质组学显示，在 C8C3 中，与 C8C3 相比，有 1547 种鉴定蛋白中有 390 种蛋白差异调节。其中，C8C3 中有 174 种蛋白上调，C8C3 中有 216 种蛋白下调。C8C3 中上调的蛋白与三羧酸循环、核糖体蛋白和氧化还原蛋白有关。C8C3 中表达的 Czp、CRP、TS、Tc-85 和唾液酸化表位水平高于 C8C3。因此， 毒力可能与毒力因子表达以及生物能量和生物合成途径蛋白的上调有关。
