Laboratório de Pesquisa em Malária, Instituto Oswaldo Cruz, Fiocruz and Centro de Pesquisa, Diagnóstico e Treinamento em Malária (CPD-Mal), Secretaria de Vigilância em Saúde e Ambiente (SVSA), Ministério da Saúde, Rio de Janeiro, Brasil.
Instituto Leônidas e Maria Deane, Fiocruz Amazônia, Manaus, Brasil.
Mol Biol Rep. 2024 Apr 29;51(1):594. doi: 10.1007/s11033-024-09538-x.
Metacaspases comprise a family of cysteine proteases implicated in both cell death and cell differentiation of protists that has been considered a potential drug target for protozoan parasites. However, the biology of metacaspases in Plasmodium vivax - the second most prevalent and most widespread human malaria parasite worldwide, whose occurrence of chemoresistance has been reported in many endemic countries, remains largely unexplored. Therefore, the present study aimed to address, for the first time, the expression pattern of metacaspases in P. vivax parasites.
P. vivax blood-stage parasites were obtained from malaria patients in the Brazilian Amazon and the expression of the three putative P. vivax metacaspases (PvMCA1-3) was detected in all isolates by quantitative PCR assay. Of note, the expression levels of each PvMCA varied noticeably across isolates, which presented different frequencies of parasite forms, supporting that PvMCAs may be expressed in a stage-specific manner as previously shown in P. falciparum.
The detection of metacaspases in P. vivax blood-stage parasites reported herein, allows the inclusion of these proteases as a potential candidate drug target for vivax malaria, while further investigations are still required to evaluate the activity, role and essentiality of metacaspases in P. vivax biology.
天冬氨酸半胱氨酸蛋白酶家族（metacaspases）参与原生动物的细胞死亡和细胞分化，被认为是原生动物寄生虫的潜在药物靶点。然而，关于引起世界范围内第二大流行和最广泛传播的人类疟疾的疟原虫——间日疟原虫（Plasmodium vivax）中天冬氨酸半胱氨酸蛋白酶的生物学特性，其研究仍基本处于空白。因此，本研究首次旨在阐明间日疟原虫中天冬氨酸半胱氨酸蛋白酶的表达模式。
从巴西亚马逊地区的疟疾患者中获得间日疟原虫血期虫体，并通过定量 PCR 检测到所有分离株中存在三种假定的间日疟原虫天冬氨酸半胱氨酸蛋白酶（PvMCA1-3）。值得注意的是，每个 PvMCA 的表达水平在不同分离株中差异明显，这表明 PvMCAs 可能以阶段特异性的方式表达，如先前在恶性疟原虫中所显示的那样。
本研究首次在间日疟原虫血期虫体中检测到天冬氨酸半胱氨酸蛋白酶，使这些蛋白酶成为间日疟的潜在候选药物靶点。然而，仍需要进一步研究来评估天冬氨酸半胱氨酸蛋白酶在间日疟原虫生物学中的活性、作用和必要性。
