A global map of genetic diversity in Babesia microti reveals strong population structure and identifies variants associated with clinical relapse
A global map of genetic diversity in Babesia microti reveals strong population structure and identifies variants associated with clinical relapse
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DOI：
10.1038/nmicrobiol.2016.79
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发表时间：
2016-07-01
影响因子：
28.3
通讯作者：
Sabeti, Pardis C.
中科院分区：
文献类型：
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作者：
Lemieux, Jacob E.;Tran, Alice D.;Sabeti, Pardis C.
由田鼠巴贝斯虫引起的人类巴贝斯虫病是一种新兴的蜱传人畜共患病，由于其发病率上升和地理范围不断扩大，其重要性日益增加(1)。这种生物体是顶复门的红细胞内寄生虫，感染后会引起类似于疟疾的发热综合征(2)。疾病复发在免疫功能低下和无脾个体中很常见(3,4)，最近有报道称耐药性(5)。为了研究这种寄生虫的起源和遗传多样性，我们对来自世界各地的 42 个田鼠小蜱样本的完整基因组进行了测序，其中包括美国大陆流行地区临床感染的深度覆盖。来自美国大陆的样本分为东北部系和中西部部系，随后亚种群沿地理线出现分歧。我们鉴定了与复发性疾病相关的寄生虫变异，包括细胞色素 b (cytb) 的阿托伐醌结合区和核糖体蛋白亚基 L4 (rpl4) 的阿奇霉素结合区的氨基酸取代。我们的研究结果揭示了田鼠芽孢杆菌的起源、多样性和进化，提出了临床复发的可能机制，并为进一步研究这种新兴病原体奠定了基础。
Human babesiosis caused by Babesia microti is an emerging tick-borne zoonosis of increasing importance due to its rising incidence and expanding geographic range(1). Infection with this organism, an intraerythrocytic parasite of the phylum Apicomplexa, causes a febrile syndrome similar to malaria(2). Relapsing disease is common among immunocompromised and asplenic individuals(3,4) and drug resistance has recently been reported(5). To investigate the origin and genetic diversity of this parasite, we sequenced the complete genomes of 42 B. microti samples from around the world, including deep coverage of clinical infections at endemic sites in the continental USA. Samples from the continental USA segregate into a Northeast lineage and a Midwest lineage, with subsequent divergence of subpopulations along geographic lines. We identify parasite variants that associate with relapsing disease, including amino acid substitutions in the atovaquone-binding regions of cytochrome b (cytb) and the azithromycin-binding region of ribosomal protein subunit L4 (rpl4). Our results shed light on the origin, diversity and evolution of B. microti, suggest possible mechanisms for clinical relapse, and create the foundation for further research on this emerging pathogen.