Department of Internal Medicine, Section of Infectious Diseases, Yale School of Medicine, New Haven, CT 06520, USA.
Department of Statistics, University of California, 900 University Avenue, Riverside, CA 92521, USA.
Int J Parasitol. 2019 Feb;49(2):105-113. doi: 10.1016/j.ijpara.2018.05.008. Epub 2018 Aug 31.
Babesia microti and Babesia duncani are the main causative agents of human babesiosis in the United States. While significant knowledge about B. microti has been gained over the past few years, nothing is known about B. duncani biology, pathogenesis, mode of transmission or sensitivity to currently recommended therapies. Studies in immunocompetent wild type mice and hamsters have shown that unlike B. microti, infection with B. duncani results in severe pathology and ultimately death. The parasite factors involved in B. duncani virulence remain unknown. Here we report the first known completed sequence and annotation of the apicoplast and mitochondrial genomes of B. duncani. We found that the apicoplast genome of this parasite consists of a 34 kb monocistronic circular molecule encoding functions that are important for apicoplast gene transcription as well as translation and maturation of the organelle's proteins. The mitochondrial genome of B. duncani consists of a 5.9 kb monocistronic linear molecule with two inverted repeats of 48 bp at both ends. Using the conserved cytochrome b (Cytb) and cytochrome c oxidase subunit I (coxI) proteins encoded by the mitochondrial genome, phylogenetic analysis revealed that B. duncani defines a new lineage among apicomplexan parasites distinct from B. microti, Babesia bovis, Theileria spp. and Plasmodium spp. Annotation of the apicoplast and mitochondrial genomes of B. duncani identified targets for development of effective therapies. Our studies set the stage for evaluation of the efficacy of these drugs alone or in combination against B. duncani in culture as well as in animal models.
微小巴贝斯虫和邓肯巴贝斯虫是美国人类巴贝斯虫病的主要病原体。虽然过去几年对微小巴贝斯虫有了相当多的了解，但对邓肯巴贝斯虫的生物学、发病机制、传播方式或对目前推荐的治疗方法的敏感性一无所知。在免疫功能正常的野生型小鼠和仓鼠中的研究表明，与微小巴贝斯虫不同，感染邓肯巴贝斯虫会导致严重的病理和最终死亡。导致邓肯巴贝斯虫毒力的寄生虫因素尚不清楚。在这里，我们报告了第一个已知的完整序列和巴贝斯虫的质体基因组和线粒体基因组的注释。我们发现，这种寄生虫的质体基因组由一个 34kb 的单顺反子环状分子组成，编码对质体基因转录以及细胞器蛋白质的翻译和成熟很重要的功能。巴贝斯虫的线粒体基因组由一个 5.9kb 的单顺反子线性分子组成，两端有两个 48bp 的反向重复。利用线粒体基因组编码的保守细胞色素 b（Cytb）和细胞色素 c 氧化酶亚基 I（coxI）蛋白进行系统发育分析表明，巴贝斯虫定义了一种新的线系，与微小巴贝斯虫、牛巴贝斯虫、泰勒虫属和疟原虫属不同。巴贝斯虫的质体基因组和线粒体基因组的注释为开发有效治疗方法确定了靶点。我们的研究为评估这些药物单独或联合在体外以及动物模型中对巴贝斯虫的疗效奠定了基础。
