Abstract：
Babesia gibsoni is mainly transmitted by hard ticks of the genus Rhipicephalus (R. sanguineus) and Haemaphysalis (H. longicornis), and causes canine babesiosis. Clinical manifestations of B. gibsoni infection include fever, hemoglobinemia, hemoglobinuria, and progressive anemia. Traditional antibabesial therapy, such as imidocarb dipropionate or diminazene aceturate, can only alleviate severe clinical manifestations and cannot eliminate parasites in the host. Food and Drug Administration (FDA)-approved drugs are a solid starting point for researching novel therapy strategies for canine babesiosis. In this work, we screened 640 FDA-approved drugs against the growth of B. gibsoni in vitro. Among them, 13 compounds (at 10 μM) exhibited high growth inhibition (>60%), and two compounds, namely idarubicin hydrochloride (idamycin) and vorinostat, were chosen for further investigation. The half-maximal inhibitory concentration (IC50) values of idamycin and vorinostat were determined to be 0.044 ± 0.008 μM and 0.591 ± 0.107 μM, respectively. Viability results indicated that a concentration of 4 × IC50 of vorinostat prevented the regrowth of treated B. gibsoni, whereas parasites treated with 4 × IC50 concentration of idamycin remained viable. The B. gibsoni parasites treated with vorinostat exhibited degeneration within erythrocytes and merozoites, in contrast to the oval or signet-ring shape of normal B. gibsoni parasites. In conclusion, FDA-approved drugs offer a valuable platform for drug repositioning in antibabesiosis research. Particularly, vorinostat demonstrated promising inhibitory effects against B. gibsoni in vitro, and further studies on vorinostat are necessary to elucidate its mechanism as a novel treatment in infected animal models.
摘要：
gibsoni巴贝斯主要由Rhipicephalus属的硬蜱传播（R.血根病)和血根病(H.longicornis)，并导致犬巴贝斯虫病。Gibsoni感染的临床表现包括发热，血红蛋白血症,血红蛋白尿症,和进行性贫血。传统的抗菌疗法，例如二丙酸亚胺酯或乙酰苯那嗪，只能缓解严重的临床表现，不能消除宿主中的寄生虫。食品和药物管理局（FDA）批准的药物是研究犬巴贝斯虫病新治疗策略的坚实起点。在这项工作中,我们在体外筛选了640种FDA批准的药物来抑制吉布索尼杆菌的生长。其中,13种化合物（10μM）表现出高生长抑制（>60％），和两种化合物，即盐酸伊达比星（伊达霉素）和伏立诺他，被选中作进一步调查。伊达霉素和伏立诺他的半最大抑制浓度（IC50）值确定为0.044±0.008μM和0.591±0.107μM，分别。生存力结果表明，伏立诺他的浓度为4×IC50，可以防止处理过的双歧杆菌的再生长。而用4×IC50浓度的伊达霉素处理的寄生虫仍然存活。用伏立诺他治疗的B.gibsoni寄生虫在红细胞和裂殖子内表现出变性，与正常B.gibsoni寄生虫的椭圆形或印戒形状相反。总之,FDA批准的药物为抗巴贝斯虫病研究中的药物重新定位提供了有价值的平台。特别是,伏立诺他在体外对双歧杆菌表现出了有希望的抑制作用，对伏立诺他的进一步研究对于阐明其在感染动物模型中作为新型治疗方法的机制是必要的。
