病原白色念珠球菌及宿主斑馬魚交互作用之動態轉錄因子分析

Dynamic transcriptomic analysis of Candida albicans and zebrafish host interactions

陳彥宇

指導教授 ： 汪上曉

國立清華大學/工學院/化學工程學系/博士(2013年)

摘要

The interactions between a fungal pathogen and its host are a complex and dynamic process. This present work adopted a systems biology approach to investigate a Candida albicans infection in a host zebrafish model. We sampled surviving fish at various post-infection times to obtain transcriptome microarray data and to conduct histological analyses. Principal component analysis (PCA) was used to analyze dynamic variations in significant gene expression profiles in C. albicans and zebrafish. PCA results indicated that C. albicans infection occurs in three distinct stages: the adhesion, invasion, and damage phases. Our findings were supported by histological analysis results. We found that in both C. albicans and zebrafish, the primary ontological function of genes exhibiting significant variation is iron-related. During the invasion and damage phases, C. albicans overexpressed most of its iron-related genes, whereas zebrafish suppressed most of these genes during the same periods. Zebrafish shut down iron homeostasis control after massive hemorrhage during the later stages of infection, during which C. albicans activated its own iron scavenging function, suggesting competition for iron between the host and its fungal pathogen during infection. Our findings provide evidence for the dynamic iron competition mechanisms and identify potential regulatory processes that occur during fungal pathogenesis.

關鍵字

白色念珠球菌 ； 斑馬魚 ； 動態轉錄因子分析

並列摘要

The interactions between a fungal pathogen and its host are a complex and dynamic process. This present work adopted a systems biology approach to investigate a Candida albicans infection in a host zebrafish model. We sampled surviving fish at various post-infection times to obtain transcriptome microarray data and to conduct histological analyses. Principal component analysis (PCA) was used to analyze dynamic variations in significant gene expression profiles in C. albicans and zebrafish. PCA results indicated that C. albicans infection occurs in three distinct stages: the adhesion, invasion, and damage phases. Our findings were supported by histological analysis results. We found that in both C. albicans and zebrafish, the primary ontological function of genes exhibiting significant variation is iron-related. During the invasion and damage phases, C. albicans overexpressed most of its iron-related genes, whereas zebrafish suppressed most of these genes during the same periods. Zebrafish shut down iron homeostasis control after massive hemorrhage during the later stages of infection, during which C. albicans activated its own iron scavenging function, suggesting competition for iron between the host and its fungal pathogen during infection. Our findings provide evidence for the dynamic iron competition mechanisms and identify potential regulatory processes that occur during fungal pathogenesis.

並列關鍵字

Candida albicans ； Zebrafish ； Dynamic interspecies transcriptomic analysis

參考文獻

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