Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório Interdisciplinar de Pesquisas Médicas, Rio de Janeiro, RJ, Brasil.
Universidade do Estado do Rio de Janeiro, Faculdade de Ciências Médicas, Disciplina de Parasitologia, Rio de Janeiro, RJ, Brasil.
Mem Inst Oswaldo Cruz. 2020 Nov 2;115:e200303. doi: 10.1590/0074-02760200303. eCollection 2020.
Giardiasis is an infectious disease caused by Giardia duodenalis. The pro-drug metronidazole (MTZ) is the first-line treatment for giardiasis. Parasite's proteins as pyruvate:ferredoxin oxidoreductase (PFOR), ferredoxin (Fd), nitroreductase-1 (NR-1) and thioredoxin reductase (TrxR) participate in MTZ activation. Here, we showed Giardia trophozoites long-term exposed to MTZ presented higher IC50 than controls, showing the drug influenced the parasite survival. That reduction in MTZ's susceptibility does not seem to be related to mutations in the genes pfor, fd, nr-1 or trxr. It points that different mechanism as alterations in other metabolic pathways can account for Giardia resistance to MTZ therapy.
贾第虫病是由蓝氏贾第鞭毛虫引起的传染病。前药甲硝唑（MTZ）是贾第虫病的一线治疗药物。寄生虫的蛋白质如丙酮酸：铁氧还蛋白氧化还原酶（PFOR）、铁氧还蛋白（Fd）、硝基还原酶-1（NR-1）和硫氧还蛋白还原酶（TrxR）参与 MTZ 的激活。在这里，我们表明，长期暴露于 MTZ 的滋养体贾第虫表现出比对照更高的 IC50，表明药物影响了寄生虫的存活。这种对 MTZ 敏感性的降低似乎与 pfor、fd、nr-1 或 trxr 基因的突变无关。这表明不同的机制，如其他代谢途径的改变，可以解释贾第虫对 MTZ 治疗的耐药性。
