National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Parasitol Res. 2019 Oct;118(10):3001-3010. doi: 10.1007/s00436-019-06449-w. Epub 2019 Sep 5.
Neospora caninum is an apicomplexan parasite considered one of the main causes of abortion in cattle worldwide; thus, there is an urgent need to develop novel therapeutic agents to control the neosporosis. Enoyl acyl carrier protein reductase (ENR) is a key enzyme of the type II fatty acid synthesis pathway (FAS II), which is essential for apicomplexan parasite survival. The antimicrobial agent triclosan has been shown to be a very potent inhibitor of ENR. In this study, we identified an E. coli ENR-like protein in N. caninum. Multiple sequence alignment showed all the requisite features of ENR existed in this protein, so we named this protein NcENR. Swiss-Model analysis showed NcENR interacts with triclosan. We observed that ENR is localized in the apicoplast, a plastid-like organelle. Similar to the potent inhibition of triclosan on other apicomplexa parasites, this compound markedly inhibits the growth of N. caninum at low concentrations. Further research showed that triclosan attenuated the invasion ability and proliferation ability of N. caninum at low concentrations. The results from in vivo studies in the mouse showed that triclosan attenuated the virulence of N. caninum in mice mildly and reduced the parasite burden in the brain significantly. Taken together, triclosan inhibits the growth of N. caninum both in vitro and in vivo at low concentrations.
刚地弓形虫是一种顶复门寄生虫，被认为是全世界牛流产的主要原因之一；因此，迫切需要开发新的治疗药物来控制弓形虫病。烯酰基辅酶 A 还原酶（ENR）是 II 型脂肪酸合成途径（FAS II）的关键酶，对顶复门寄生虫的生存至关重要。抗菌剂三氯生已被证明是 ENR 的非常有效的抑制剂。在这项研究中，我们在刚地弓形虫中鉴定出一种大肠杆菌 ENR 样蛋白。多重序列比对显示该蛋白存在 ENR 的所有必需特征，因此我们将该蛋白命名为 NcENR。Swiss-Model 分析表明 NcENR 与三氯生相互作用。我们观察到 ENR 定位于类质体，一种类似于质体的细胞器。与三氯生对其他顶复门寄生虫的强烈抑制作用类似，该化合物在低浓度下显著抑制刚地弓形虫的生长。进一步的研究表明，三氯生在低浓度下可减弱刚地弓形虫的侵袭能力和增殖能力。在小鼠体内研究的结果表明，三氯生在轻度减弱刚地弓形虫对小鼠的毒力的同时，显著降低了脑中寄生虫的负荷。综上所述，三氯生在低浓度下可在体外和体内抑制刚地弓形虫的生长。
