Abstract：
Acanthamoeba species are among the most ubiquitous protists that are widespread in soil and water and act as both a replicative niche and vectors for dispersal. They are the most important human intracellular pathogens, causing Acanthamoeba keratitis (AK) and severely damaging the human cornea. The sympatric lifestyle within the host and amoeba-resisting microorganisms (ARMs) promotes horizontal gene transfer (HGT). However, the genomic diversity of only A. castellanii and A. polyphaga has been widely studied, and the pathogenic mechanisms remain unknown. Thus, we examined 7 clinically pathogenic strains by comparative genomic, phylogenetic, and rhizome gene mosaicism analyses to explore amoeba-symbiont interactions that possibly contribute to pathogenesis. Genetic characterization and phylogenetic analysis showed differences in functional characteristics between the \"open\" state of T3 and T4 isolates, which may contribute to the differences in virulence and pathogenicity. Through comparative genomic analysis, we identified potential genes related to virulence, such as metalloprotease, laminin-binding protein, and HSP, that were specific to the genus Acanthamoeba. Then, analysis of putative sequence trafficking between Acanthamoeba and Pandoraviruses or Acanthamoeba castellanii medusaviruses provided the best hits with viral genes; among bacteria, Pseudomonas had the most significant numbers. The most parsimonious evolutionary scenarios were between Acanthamoeba and endosymbionts; nevertheless, in most cases, the scenarios are more complex. In addition, the differences in exchanged genes were limited to the same family. In brief, this study provided extensive data to suggest the existence of HGT between Acanthamoeba and ARMs, explaining the occurrence of diseases and challenging Darwin\'s concept of eukaryotic evolution. IMPORTANCE Acanthamoeba has the ability to cause serious blinding keratitis. Although the prevalence of this phenomenon has increased in recent years, our knowledge of the underlying opportunistic pathogenic mechanism maybe remains incomplete. In this study, we highlighted the importance of Pseudomonas in the pathogenesis pathway using comprehensive a whole genomics approach of clinical isolates. The horizontal gene transfer events help to explain how endosymbionts contribute Acanthamoeba to act as an opportunistic pathogen. Our study opens up several potential avenues for future research on the differences in pathogenicity and interactions among clinical strains.
摘要：
棘阿米巴物种是最普遍的原生生物之一，广泛存在于土壤和水中，既是复制性的生态位又是传播的媒介。它们是人类最重要的细胞内病原体，导致棘阿米巴角膜炎（AK）并严重损害人类角膜。宿主内的同胞生活方式和抗变形虫微生物（ARM）促进水平基因转移（HGT）。然而,只有A.castellanii和A.polyphaga的基因组多样性已被广泛研究，致病机制仍然未知。因此，我们通过比较基因组检查了7种临床致病菌株，系统发育，和根茎基因镶嵌分析，以探索变形虫-共生体相互作用，可能有助于发病机制。遗传特征和系统发育分析表明，T3和T4分离株的“开放”状态之间的功能特征存在差异，这可能导致毒力和致病性的差异。通过比较基因组分析，我们确定了与毒力相关的潜在基因，如金属蛋白酶，层粘连蛋白结合蛋白，和HSP,是棘阿米巴属特有的。然后，分析棘阿米巴和潘多拉病毒之间的推定序列运输或马卡斯特兰病毒提供了病毒基因的最佳命中；在细菌中，假单胞菌的数量最显著。最简约的进化情景是在棘阿米巴和内共生体之间；尽管如此，在大多数情况下,场景更加复杂。此外,交换基因的差异仅限于同一家族。简而言之,这项研究提供了大量数据，表明棘阿米巴和ARM之间存在HGT，解释疾病的发生并挑战达尔文的真核进化概念。重要性棘阿米巴具有引起严重致盲性角膜炎的能力。尽管近年来这种现象的患病率有所增加，我们对潜在的机会致病机制的了解可能仍然不完整。在这项研究中,我们通过对临床分离株进行全面的全基因组学研究,强调了假单胞菌在发病途径中的重要性.水平基因转移事件有助于解释内共生体如何使棘阿米巴成为机会性病原体。我们的研究为未来研究临床菌株之间的致病性和相互作用的差异开辟了几个潜在的途径。
