Whole genome sequencing shows sleeping sickness relapse is due to parasite regrowth and not reinfection.
Whole genome sequencing shows sleeping sickness relapse is due to parasite regrowth and not reinfection.
复制标题
全基因组测序显示昏睡病复发是由于寄生虫重新生长而不是再次感染造成的。
DOI：
10.1111/eva.12338
复制
发表时间：
2016
影响因子：
4.1
通讯作者：
Caccone,Adalgisa
中科院分区：
文献类型：
--
作者：
Richardson,JoshuaB;Evans,Benjamin;Pyana,PatientP;VanReet,Nick;Sistrom,Mark;Büscher,Philippe;Aksoy,Serap;Caccone,Adalgisa
布氏冈比亚锥虫（Trypanosoma brucei gambiense，Tbg）是撒哈拉以南非洲许多地区特有的人类非洲锥虫病（HAT）的病因。这种疾病如果得不到治疗，几乎总是致命的，而且没有疫苗，这使得监测和管理耐药性具有高度相关性。最近对来自刚果民主共和国的HAT病例进行的一项研究报告，接受美拉胂醇治疗的患者复发率较高。在从本研究中登记的患者中分离的19株Tbg菌株中，4对是在治疗前和复发后从同一患者获得的。我们使用全基因组测序来调查这些患者是否感染了新菌株，或者原始菌株是否重新生长到致病水平。对5938个单核苷酸多态性的聚类分析支持原始菌株再生的假设，因为我们发现从同一患者治疗前后分离的菌株彼此之间比其他菌株更相似。我们还确定了23个可能影响美拉胂醇敏感性的新基因，为未来的功能研究提供了一组有希望的新靶点。这项工作证明了使用进化方法为疾病控制提供新的见解和工具的实用性。
The trypanosomeTrypanosoma brucei gambiense(Tbg) is a cause of human African trypanosomiasis (HAT) endemic to many parts of sub‐Saharan Africa. The disease is almost invariably fatal if untreated and there is no vaccine, which makes monitoring and managing drug resistance highly relevant. A recent study of HAT cases from the Democratic Republic of the Congo reported a high incidence of relapses in patients treated with melarsoprol. Of the 19Tbgstrains isolated from patients enrolled in this study, four pairs were obtained from the same patient before treatment and after relapse. We used whole genome sequencing to investigate whether these patients were infected with a new strain, or if the original strain had regrown to pathogenic levels. Clustering analysis of 5938 single nucleotide polymorphisms supports the hypothesis of regrowth of the original strain, as we found that strains isolated before and after treatment from the same patient were more similar to each other than to other isolates. We also identified 23 novel genes that could affect melarsoprol sensitivity, representing a promising new set of targets for future functional studies. This work exemplifies the utility of using evolutionary approaches to provide novel insights and tools for disease control.