Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
J Eukaryot Microbiol. 2013 Mar-Apr;60(2):179-91. doi: 10.1111/jeu.12022. Epub 2013 Jan 29.
Naegleria fowleri is a unicellular eukaryote causing primary amoebic meningoencephalitis, a neuropathic disease killing 99% of those infected, usually within 7-14 days. Naegleria fowleri is found globally in regions including the US and Australia. The genome of the related nonpathogenic species Naegleria gruberi has been sequenced, but the genetic basis for N. fowleri pathogenicity is unclear. To generate such insight, we sequenced and assembled the mitochondrial genome and a 60-kb segment of nuclear genome from N. fowleri. The mitochondrial genome is highly similar to its counterpart in N. gruberi in gene complement and organization, while distinct lack of synteny is observed for the nuclear segments. Even in this short (60-kb) segment, we identified examples of potential factors for pathogenesis, including ten novel N. fowleri-specific genes. We also identified a homolog of cathepsin B; proteases proposed to be involved in the pathogenesis of diverse eukaryotic pathogens, including N. fowleri. Finally, we demonstrate a likely case of horizontal gene transfer between N. fowleri and two unrelated amoebae, one of which causes granulomatous amoebic encephalitis. This initial look into the N. fowleri nuclear genome has revealed several examples of potential pathogenesis factors, improving our understanding of a neglected pathogen of increasing global importance.
福氏耐格里阿米巴是一种单细胞真核生物,可引起原发性阿米巴脑膜脑炎,这是一种神经疾病,感染后 99%的患者通常在 7-14 天内死亡。福氏耐格里阿米巴在全球范围内的美国和澳大利亚等地区都有发现。相关的非致病性物种纳格里亚 gruberi 的基因组已经测序,但福氏耐格里阿米巴致病性的遗传基础尚不清楚。为了获得这种洞察力,我们对福氏耐格里阿米巴的线粒体基因组和 60kb 的核基因组片段进行了测序和组装。线粒体基因组在基因组成和组织上与纳格里亚 gruberi 的对应物非常相似,而核片段的基因排列则明显缺乏同线性。即使在这个短的(60kb)片段中,我们也发现了一些可能与发病机制有关的因素,包括 10 个新的福氏耐格里阿米巴特异性基因。我们还鉴定了组织蛋白酶 B 的同源物;蛋白酶被认为参与了包括福氏耐格里阿米巴在内的多种真核病原体的发病机制。最后,我们证明了福氏耐格里阿米巴与两种不相关的变形虫之间可能存在水平基因转移,其中一种变形虫可引起肉芽肿性阿米巴脑炎。对福氏耐格里阿米巴核基因组的初步研究揭示了几个可能的发病机制因素,提高了我们对这种被忽视的、具有日益重要的全球意义的病原体的认识。