Institute of Parasitology, Biomedical Research Center Seltersberg, Justus Liebig University Giessen, 35392Giessen, Germany.
Parasitology. 2021 Aug;148(9):1107-1115. doi: 10.1017/S0031182021000822. Epub 2021 May 24.
Coccidia are obligate apicomplexan parasites that affect humans and animals. In fast replicating species, in vitro merogony takes only 24–48 h. In this context, successful parasite proliferation requires nutrients and other building blocks. Coccidian parasites are auxotrophic for cholesterol, so they need to obtain this molecule from host cells. In humans, ezetimibe has been applied successfully as hypolipidaemic compound, since it reduces intestinal cholesterol absorption via blockage of Niemann−Pick C-1 like-1 protein (NPC1L1), a transmembrane protein expressed in enterocytes. To date, few data are available on its potential anti-parasitic effects in primary host cells infected with apicomplexan parasites of human and veterinary importance, such as Toxoplasma gondii, Neospora caninum and Besnoitia besnoiti. Current inhibition experiments show that ezetimibe effectively blocks T. gondii, B. besnoiti and N. caninum tachyzoite infectivity and replication in primary bovine endothelial host cells. Thus, 20 μm ezetimibe blocked parasite proliferation by 73.1−99.2%, via marked reduction of the number of tachyzoites per meront, confirmed by 3D-holotomographic analyses. The effects were parasitostatic since withdrawal of the compound led to parasite recovery with resumed proliferation. Ezetimibe-glucuronide, the in vivo most effective metabolite, failed to affect parasite proliferation in vitro, thereby suggesting that ezetimibe effects might be NPC1L1-independent.
球虫是专性顶复门寄生虫，影响人类和动物。在快速复制的物种中，体外红细胞生成仅需 24-48 小时。在这种情况下，寄生虫的成功繁殖需要营养物质和其他构建块。球虫寄生虫对胆固醇是必需的，因此它们需要从宿主细胞中获得这种分子。在人类中，依折麦布已成功用作降脂化合物，因为它通过阻断 Niemann−Pick C-1 样蛋白 1（NPC1L1）来减少肠道胆固醇吸收，NPC1L1 是一种在肠细胞中表达的跨膜蛋白。迄今为止，关于其在原发性宿主细胞中的潜在抗寄生虫作用的数据很少，这些宿主细胞感染了对人类和兽医具有重要意义的顶复门寄生虫，如刚地弓形虫、新生隐孢子虫和贝氏隐孢子虫。目前的抑制实验表明，依折麦布可有效阻断刚地弓形虫、贝氏隐孢子虫和新生隐孢子虫速殖子在原代牛内皮宿主细胞中的感染性和复制。因此，20 μm 的依折麦布通过明显减少每个红细胞生成中的速殖子数量，将寄生虫的增殖阻断了 73.1-99.2%，通过 3D 全断层摄影分析得到了证实。这些作用是寄生虫停滞的，因为在撤去化合物后，寄生虫恢复增殖。依折麦布葡萄糖醛酸苷是体内最有效的代谢物，未能影响体外寄生虫的增殖，因此表明依折麦布的作用可能不依赖 NPC1L1。
