Institute of Biomedical Informatics, National Yang-Ming University, Taipei 11221, Taiwan.
Laboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan.
Biomed Res Int. 2014;2014:136130. doi: 10.1155/2014/136130. Epub 2014 Mar 18.
The clinical and biological significance of the study of fungal pathogen Candida albicans (C. albicans) has markedly increased. However, the explicit pathogenic and invasive mechanisms of such host-pathogen interactions have not yet been fully elucidated. Therefore, the essential functional modules involved in C. albicans-zebrafish interactions were investigated in this study. Adopting a systems biology approach, the early-stage and late-stage protein-protein interaction (PPI) networks for both C. albicans and zebrafish were constructed. By comparing PPI networks at the early and late stages of the infection process, several critical functional modules were identified in both pathogenic and defensive mechanisms. Functional modules in C. albicans, like those involved in hyphal morphogenesis, ion and small molecule transport, protein secretion, and shifts in carbon utilization, were seen to play important roles in pathogen invasion and damage caused to host cells. Moreover, the functional modules in zebrafish, such as those involved in immune response, apoptosis mechanisms, ion transport, protein secretion, and hemostasis-related processes, were found to be significant as defensive mechanisms during C. albicans infection. The essential functional modules thus determined could provide insights into the molecular mechanisms of host-pathogen interactions during the infection process and thereby devise potential therapeutic strategies to treat C. albicans infection.
本研究旨在探讨真菌病原体白色念珠菌（Candida albicans，C. albicans）与斑马鱼互作过程中的关键功能模块。采用系统生物学方法，构建了 C. albicans 和斑马鱼在感染早期和晚期的蛋白质-蛋白质互作（protein-protein interaction，PPI）网络。通过比较感染过程中早期和晚期的 PPI 网络，我们在致病和防御机制中鉴定出了几个关键的功能模块。在 C. albicans 中，一些功能模块，如菌丝形态发生、离子和小分子转运、蛋白质分泌以及碳利用的转变，在病原体入侵和宿主细胞损伤中发挥重要作用。此外，在斑马鱼中，一些功能模块，如免疫反应、细胞凋亡机制、离子转运、蛋白质分泌和止血相关过程，在 C. albicans 感染过程中作为防御机制也具有重要意义。这些确定的关键功能模块可以深入了解感染过程中宿主-病原体相互作用的分子机制，并为治疗 C. albicans 感染提供潜在的治疗策略。
