From the Department of Internal Medicine, Section of Infectious Diseases, and Yale School of Medicine, New Haven, Connecticut 06520.
BEI Resources, American Type Culture Collection, Manassas, Virginia 20110-2209.
J Biol Chem. 2018 Dec 28;293(52):19974-19981. doi: 10.1074/jbc.AC118.005771. Epub 2018 Nov 21.
Human babesiosis is an emerging tick-borne disease caused by apicomplexan parasites of the genus Clinical cases caused by have been associated with high parasite burden, severe pathology, and death. In both mice and hamsters, the parasite causes uncontrolled fulminant infections, which ultimately lead to death. Resolving these infections requires knowledge of biology, virulence, and susceptibility to anti-infectives, but little is known and further research is hindered by a lack of relevant model systems. Here, we report the first continuous culture of in human red blood cells. We show that during its asexual cycle within human erythrocytes, develops and divides to form four daughter parasites with parasitemia doubling every ∼22 h. Using this culture assay, we found that has low susceptibility to the four drugs recommended for treatment of human babesiosis, atovaquone, azithromycin, clindamycin, and quinine, with IC values ranging between 500 nm and 20 μm These data suggest that current practices are of limited effect in treating the disease. We anticipate this new disease model will set the stage for a better understanding of the biology of this parasite and will help guide better therapeutic strategies to treat associated babesiosis.
人类巴贝斯虫病是一种由顶复门寄生虫引起的新兴蜱传疾病。由引起的临床病例与高寄生虫负担、严重的病理和死亡有关。在小鼠和仓鼠中,寄生虫会导致无法控制的暴发性感染,最终导致死亡。要解决这些感染,需要了解生物学、毒力和对抗感染药物的敏感性,但目前所知甚少,进一步的研究受到缺乏相关模型系统的阻碍。在这里,我们报告了首例在人红细胞中连续培养的。我们表明,在人类红细胞内的无性循环中,发育并分裂为四个子体寄生虫,寄生虫血症每 22 小时左右翻倍。使用这种培养测定法,我们发现对四种推荐用于治疗人类巴贝斯虫病的药物(阿托伐醌、阿奇霉素、克林霉素和奎宁)的敏感性较低,IC 值在 500nm 到 20μm 之间。这些数据表明,目前的治疗方法对治疗这种疾病的效果有限。我们预计这种新的疾病模型将为更好地理解这种寄生虫的生物学奠定基础,并有助于指导更好的治疗策略来治疗相关的巴贝斯虫病。