Waterborne Disease Prevention Branch, Division of Foodborne, Waterborne, and Environmental Diseases, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Preventiongrid.416738.f, Atlanta, Georgia, USA.
Eagle Medical Services, Atlanta, Georgia, USA.
mSphere. 2021 Aug 25;6(4):e0063721. doi: 10.1128/mSphere.00637-21. Epub 2021 Aug 11.
Out of over 40 species of , which are free-living thermophilic amebae found in freshwater and soil worldwide, only Naegleria fowleri infects humans, causing primary amebic meningoencephalitis (PAM), a typically fatal brain disease. To understand the population structure of species and the genetic relationships between N. fowleri isolates and to detect pathogenic factors, we characterized 52 novel clinical and environmental N. fowleri genomes and a single Naegleria lovaniensis strain, along with transcriptomic data for a subset of 37 N. fowleri isolates. Whole-genome analysis of 56 isolates from three species (N. fowleri, , and Naegleria gruberi) identified several genes unique to N. fowleri that have previously been linked to the pathogenicity of N. fowleri, while other unique genes could be associated with novel pathogenicity factors in this highly fatal pathogen. Population structure analysis estimated the presence of 10 populations within the three species, of which 7 populations were within N. fowleri. The whole-nuclear-genome (WNG) phylogenetic analysis showed an overall geographical clustering of N. fowleri isolates, with few exceptions, and provided higher resolution in identifying potential clusters of isolates beyond that of the traditional locus typing. There were only 34 genes that showed significant differences in gene expression between the clinical and environmental isolates. Genomic data generated in this study can be used for developing rapid molecular assays and to conduct future population-based global genomic analysis and will also be a valuable addition to genomic reference databases, where shotgun metagenomics data from routine water samples could be searched for the presence of N. fowleri strains. N. fowleri, the only known species to infect humans, causes fatal brain disease. PAM cases from 1965 to 2016 showed <20 cases per year globally. Out of approximately 150 cases in North America since 1962, only four PAM survivors are known, yielding a >97% case fatality rate, which is critically high. Although the pathogenesis of N. fowleri has been studied for the last 50 years, pathogenetic factors that lead to human infection and breaching the blood-brain barrier remain unknown. In addition, little is known regarding the genomic diversity both within N. fowleri isolates and among species. In this study, we generated novel genome sequences and performed comparative genomic and transcriptomic analysis of a set of 52 N. fowleri draft genome sequences from clinical and environmental isolates derived from all over the world in the last 53 years, which will help shape future genome-wide studies and develop sensitive assays for routine surveillance.
全世界的自由生活嗜热变形虫中有超过 40 种，其中只有福氏纳格里虫会感染人类，导致原发性阿米巴脑膜脑炎（PAM），这是一种典型的致命脑部疾病。为了了解阿米巴属物种的种群结构以及福氏纳格里虫分离株之间的遗传关系，并检测致病因素，我们对 52 个新型临床和环境福氏纳格里虫基因组以及一个纳格里亚拉万尼ensis 菌株进行了特征描述，并对 37 个福氏纳格里虫分离株中的一部分进行了转录组数据。对来自三个阿米巴属物种（福氏纳格里虫、 和纳格里亚格吕伯里）的 56 个分离株的全基因组分析确定了一些以前与福氏纳格里虫的致病性相关的福氏纳格里虫特有的基因，而其他特有的基因可能与这种高致命病原体的新的致病性因素有关。种群结构分析估计，在这三个阿米巴属物种中存在 10 个种群，其中 7 个种群存在于福氏纳格里虫中。全核基因组（WNG）系统发育分析显示，福氏纳格里虫分离株总体上具有地理聚类，只有少数例外，并且在确定潜在的分离株簇方面提供了比传统基因座分型更高的分辨率。只有 34 个基因在临床和环境分离株之间的基因表达有显著差异。本研究生成的基因组数据可用于开发快速分子检测方法，并进行未来基于种群的全球基因组分析，同时还将成为基因组参考数据库的有价值补充，可在该数据库中搜索常规水样中的福氏纳格里虫菌株。 福氏纳格里虫是唯一已知感染人类的阿米巴属物种，可导致致命性脑部疾病。1965 年至 2016 年期间，全球每年 PAM 病例不到 20 例。自 1962 年以来，北美约有 150 例 PAM 幸存者，仅 4 例幸存，病死率>97%，这一比率极高。尽管福氏纳格里虫的发病机制已经研究了 50 年，但导致人类感染和突破血脑屏障的致病因素仍不清楚。此外，人们对福氏纳格里虫分离株内以及其他阿米巴属物种之间的基因组多样性知之甚少。在这项研究中，我们生成了新型基因组序列，并对来自世界各地的 52 个福氏纳格里虫临床和环境分离株的一组 52 个福氏纳格里虫草案基因组序列进行了比较基因组和转录组分析，这将有助于塑造未来的全基因组研究，并开发用于常规监测的敏感检测方法。
