Laboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan.
Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 30013, Taiwan.
Toxins (Basel). 2019 Feb 15;11(2):119. doi: 10.3390/toxins11020119.
() is the most prevalent fungal species. Although it is a healthy microbiota, genetic and epigenetic alterations in host and pathogen, and microenvironment changes would lead to thrush, vaginal yeast infection, and even hematogenously disseminated infection. Despite the fact that cytotoxicity is well-characterized, few studies discuss the genome-wide genetic and epigenetic molecular mechanisms between host and . The aim of this study is to identify drug targets and design a multiple-molecule drug to prevent the infection from . To investigate the common and specific pathogenic mechanisms in human oral epithelial OKF6/TERT-2 cells during the infection in different strains, systems modeling and big databases mining were used to construct candidate host⁻pathogen genetic and epigenetic interspecies network (GEIN). System identification and system order detection are applied on two-sided next generation sequencing (NGS) data to build real host⁻pathogen cross-talk GEINs. Core host⁻pathogen cross-talk networks (HPCNs) are extracted by principal network projection (PNP) method. By comparing with core HPCNs in different strains of , common pathogenic mechanisms were investigated and several drug targets were suggested as follows: orf19.5034 (YBP1) with the ability of anti-ROS; orf19.939 (NAM7), orf19.2087 (SAS2), orf19.1093 (FLO8) and orf19.1854 (HHF22) with high correlation to the hyphae growth and pathogen protein interaction; orf19.5585 (SAP5), orf19.5542 (SAP6) and orf19.4519 (SUV3) with the cause of biofilm formation. Eventually, five corresponding compounds-Tunicamycin, Terbinafine, Cerulenin, Tetracycline and Tetrandrine-with three known drugs could be considered as a potential multiple-molecule drug for therapeutic treatment of .
白色念珠菌是最普遍的真菌物种。尽管它是一种健康的微生物群，但宿主和病原体的遗传和表观遗传改变以及微环境变化会导致鹅口疮、阴道酵母菌感染，甚至血源性播散性感染。尽管细胞毒性已得到充分研究，但很少有研究探讨宿主和之间全基因组遗传和表观遗传分子机制。本研究旨在确定药物靶点并设计一种多分子药物来预防感染。为了研究不同菌株中人类口腔上皮 OKF6/TERT-2 细胞感染期间的共同和特异致病机制，使用系统建模和大数据挖掘构建候选宿主-病原体遗传和表观遗传种间网络（GEIN）。双边下一代测序（NGS）数据的系统识别和系统阶数检测用于构建真实的宿主-病原体交叉对话 GEIN。通过主网络投影（PNP）方法提取核心宿主-病原体交叉对话网络（HPCN）。通过比较不同菌株的核心 HPCN，研究了共同的致病机制，并提出了几个药物靶点，如下所示：orf19.5034（YBP1）具有抗 ROS 能力；orf19.939（NAM7）、orf19.2087（SAS2）、orf19.2087（SAS2）、orf19.1093（FLO8）和 orf19.1854（HHF22）与菌丝生长和病原体蛋白相互作用高度相关；orf19.5585（SAP5）、orf19.5542（SAP6）和 orf19.4519（SUV3）与生物膜形成有关。最终，可以考虑五种相应的化合物——棉子糖、特比萘芬、杆菌肽、四环素和汉防己甲素——与三种已知药物一起作为治疗的潜在多分子药物。
