Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
PLoS One. 2013 Sep 3;8(9):e72483. doi: 10.1371/journal.pone.0072483. eCollection 2013.
Candida albicans is responsible for a number of life-threatening infections and causes considerable morbidity and mortality in immunocompromised patients. Previous studies of C. albicans pathogenesis have suggested several steps must occur before virulent infection, including early adhesion, invasion, and late tissue damage. However, the mechanism that triggers C. albicans transformation from yeast to hyphae form during infection has yet to be fully elucidated. This study used a systems biology approach to investigate C. albicans infection in zebrafish. The surviving fish were sampled at different post-infection time points to obtain time-lapsed, genome-wide transcriptomic data from both organisms, which were accompanied with in sync histological analyses. Principal component analysis (PCA) was used to analyze the dynamic gene expression profiles of significant variations in both C. albicans and zebrafish. The results categorized C. albicans infection into three progressing phases: adhesion, invasion, and damage. Such findings were highly supported by the corresponding histological analysis. Furthermore, the dynamic interspecies transcript profiling revealed that C. albicans activated its filamentous formation during invasion and the iron scavenging functions during the damage phases, whereas zebrafish ceased its iron homeostasis function following massive hemorrhage during the later stages of infection. Most of the immune related genes were expressed as the infection progressed from invasion to the damage phase. Such global, inter-species evidence of virulence-immune and iron competition dynamics during C. albicans infection could be crucial in understanding control fungal pathogenesis.
白色念珠菌可引发多种危及生命的感染，令免疫功能低下的患者发病率和死亡率显著升高。此前对白色念珠菌发病机制的研究表明，在发生致命感染之前，必须经历多个步骤，包括早期黏附、侵袭和晚期组织损伤。然而，白色念珠菌在感染过程中从酵母相转化为菌丝相的触发机制尚未完全阐明。本研究采用系统生物学方法，在斑马鱼体内研究白色念珠菌感染。对不同时间点感染后的存活鱼进行采样，获得来自两种生物的时程、全基因组转录组数据，并同步进行组织学分析。主成分分析（PCA）用于分析白色念珠菌和斑马鱼中显著变化的动态基因表达谱。结果将白色念珠菌感染分为三个进展阶段：黏附、侵袭和损伤。这些发现与相应的组织学分析高度吻合。此外，种间转录组的动态变化揭示，白色念珠菌在侵袭过程中激活其丝状形成，在损伤阶段激活铁摄取功能，而斑马鱼在感染后期发生大量出血后，其铁稳态功能停止。随着感染从侵袭阶段向损伤阶段进展，大多数免疫相关基因的表达也随之增加。这种白色念珠菌感染过程中毒力-免疫和铁竞争动态的全面、种间证据，对于理解真菌感染发病机制的控制至关重要。
