Dynamic Transcript Profiling of Candida Albicans Infection in Zebrafish: a Pathogen-Host Interaction Study

Dynamic Transcript Profiling of Candida Albicans Infection in Zebrafish: a Pathogen-Host Interaction Study
Yan Yu Chen, Chun-Cheih Chao, Fu-Chen Liu, Po-Chen Hsu, Hsueh-Fen Chen, Shih-Chi Peng, Yung-Jen Chuang, Chung-Yu Lan, Wen-Ping Hsieh, David Shan Hill Wong
(Submitted on 14 Jun 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. This was followed by massive hemorrhaging toward the end stage 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.


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