Martviset Pongsakorn, Chantree Pathanin, Chaimon Salisa, Torungkitmangmi Nattaya, Prathaphan Parisa, Ruangtong Jittiporn, Sornchuer Phornphan, Thongsepee Nattaya, Sangpairoj Kant, Adisakwattana Poom
Department of Preclinical Science, Faculty of Medicine, Thammasat University, Pathumthani 12120, Thailand.
Thammasat University Research Unit in Nutraceuticals and Food Safety, Thammasat University, Pathumthani 12120, Thailand.
Pathogens. 2022 Dec 1;11(12):1458. doi: 10.3390/pathogens11121458.
Fasciola gigantica, a giant liver fluke, causes tremendous loss to the livestock economy in several regions throughout the world. The situation of drug resistance has been emerging increasingly; therefore, novel drugs and drug targets need to be discovered. The adult F. gigantica inhabits the major bile ducts where bile salts accumulate—these are steroid-like molecules that mediate several physiological processes in organisms through interacting with their specific nuclear receptors. However, the molecular mechanism of the interaction in the parasitic organisms have not been clearly understood. In this study, putative nuclear receptor subfamily 1 of F. gigantica (FgNR1) was identified. Nucleotide and amino acid sequences of the FgNR1 homolog were obtained from the transcriptome of F. gigantica and predicted for properties and functions using bioinformatics. The full-length cDNA was cloned and expressed in the bacterial expression system and then used for immunization. Western analysis and immunolocalization suggested that FgNR1 could be detected in the crude worm antigens and was highly expressed in the caeca and testes of the adult parasite. Moreover, the bile could significantly activate the expression of FgNR1 in cultured parasites. Our results indicated that FgNR1 has high potential for the development of a novel anthelminthic drug in the future.
巨片形吸虫是一种大型肝吸虫,在全球多个地区给畜牧业经济造成了巨大损失。耐药性情况日益凸显,因此需要发现新型药物和药物靶点。巨片形吸虫成虫栖息在胆汁盐积聚的主要胆管中,胆汁盐是类固醇样分子,通过与特定核受体相互作用介导生物体中的多种生理过程。然而,寄生虫体内这种相互作用的分子机制尚未完全清楚。在本研究中,鉴定了巨片形吸虫假定的核受体亚家族1(FgNR1)。从巨片形吸虫转录组中获得FgNR1同源物的核苷酸和氨基酸序列,并使用生物信息学预测其性质和功能。克隆全长cDNA并在细菌表达系统中表达,然后用于免疫。Western分析和免疫定位表明,FgNR1可在虫体粗抗原中检测到,且在成虫的盲肠和睾丸中高表达。此外,胆汁可显著激活培养寄生虫中FgNR1的表达。我们的结果表明,FgNR1在未来新型抗蠕虫药物开发方面具有很高的潜力。