Department of Pathology, School of Medicine, University of California-San Diego, San Diego, CA, USA.
Int J Antimicrob Agents. 2012 Mar;39(3):259-62. doi: 10.1016/j.ijantimicag.2011.09.026. Epub 2011 Nov 21.
Tritrichomonas foetus is a sexually transmitted protozoon that causes genital inflammation and adverse pregnancy outcomes in cattle. Cysteine proteinases (CPs) released by T. foetus degrade immunoglobulin G (IgG) antibodies, complement component 3 and matrix proteins as well as inducing apoptosis of bovine genital epithelial cells. In this study, the efficacies of the vinyl sulfone CP inhibitors K11777 and WRR-483 were tested against CPs of T. foetus. The activity of secreted T. foetus CPs in culture supernatants was decreased in the presence of vinyl sulfone inhibitors. Inhibitor K11777 reduced the in vitro cytopathogenic effects of T. foetus in bovine foetal trophoblast cells, which are relevant target cells since this pathogen interferes with pregnancy. Pre-treatment of T. foetus prior to intravaginal inoculation diminished genital infection in a murine model. Therefore, vinyl sulfone CP inhibitors reduce several effects of T. foetus-secreted CPs, including cytotoxicity on relevant target host cells and genital infection in a murine model. These inhibitors have potential as chemotherapeutic agents against bovine trichomoniasis. Generalisation to human trichomoniasis requires further study.
胎儿三毛滴虫是一种性传播的原生动物，可引起牛的生殖器炎症和不良妊娠结局。胎儿三毛滴虫释放的半胱氨酸蛋白酶（CPs）可降解免疫球蛋白 G（IgG）抗体、补体成分 3 和基质蛋白，并诱导牛生殖器上皮细胞凋亡。在这项研究中，测试了乙烯砜 CP 抑制剂 K11777 和 WRR-483 对胎儿三毛滴虫 CPs 的疗效。在乙烯砜抑制剂存在的情况下，培养上清液中分泌的胎儿三毛滴虫 CPs 的活性降低。抑制剂 K11777 降低了牛胎儿滋养层细胞中胎儿三毛滴虫的体外细胞病变效应，因为这种病原体干扰了妊娠，所以这些细胞是相关的靶细胞。在阴道内接种前对胎儿三毛滴虫进行预处理可减少小鼠模型中的生殖器感染。因此，乙烯砜 CP 抑制剂可降低胎儿三毛滴虫分泌的 CPs 的多种作用，包括对相关靶宿主细胞的细胞毒性和在小鼠模型中的生殖器感染。这些抑制剂具有作为抗牛滴虫病化学治疗剂的潜力。需要进一步的研究来推广到人类滴虫病。
