Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Sci Rep. 2018 Mar 7;8(1):4135. doi: 10.1038/s41598-018-22540-1.
Pythium insidiosum is a human-pathogenic oomycete. Many patients infected with it lose organs or die. Toward the goal of developing improved treatment options, we want to understand how Py. insidiosum has evolved to become a successful human pathogen. Our approach here involved the use of comparative genomic and other analyses to identify genes with possible functions in the pathogenicity of Py. insidiosum. We generated an Oomycete Gene Table and used it to explore the genome contents and phylogenomic relationships of Py. insidiosum and 19 other oomycetes. Initial sequence analyses showed that Py. insidiosum is closely related to Pythium species that are not pathogenic to humans. Our analyses also indicated that the organism harbours secreted and adhesin-like proteins, which are absent from related species. Putative virulence proteins were identified by comparison to a set of known virulence genes. Among them is the urease Ure1, which is absent from humans and thus a potential diagnostic and therapeutic target. We used mass spectrometric data to successfully validate the expression of 30% of 14,962 predicted proteins and identify 15 body temperature (37 °C)-dependent proteins of Py. insidiosum. This work begins to unravel the determinants of pathogenicity of Py. insidiosum.
腐霉属疫霉是一种能感染人类的卵菌。许多感染该菌的患者会失去器官或死亡。为了开发更好的治疗方法，我们希望了解腐霉属疫霉是如何进化成为一种成功的人类病原体的。我们采用比较基因组学和其他分析方法，来鉴定可能与腐霉属疫霉致病有关的基因，以此作为研究手段。我们生成了一个卵菌基因表，并用它来研究腐霉属疫霉和其他 19 种卵菌的基因组内容和系统发育关系。初步的序列分析表明，腐霉属疫霉与那些对人类没有致病性的腐霉属物种密切相关。我们的分析还表明，该生物含有分泌蛋白和黏附素样蛋白，而这些蛋白在相关物种中是不存在的。通过与一组已知的毒力基因进行比较，鉴定出了推定的毒力蛋白。其中包括脲酶 Ure1，它在人类中不存在，因此是一个潜在的诊断和治疗靶点。我们使用质谱数据成功地验证了 14962 个预测蛋白中的 30%的表达，并鉴定出了腐霉属疫霉 15 种与体温（37°C）相关的蛋白。这项工作开始揭示腐霉属疫霉致病性的决定因素。
