白色念珠菌是一種人類常見的真菌性病原菌，好發於人體的口腔、皮膚、黏膜等組織，對於免疫力正常的人來說，白色念珠菌並不會引發明顯的徵狀；然而在免疫缺乏的病人身上，白色念珠菌卻會造成嚴重感染，甚至導致病人死亡。先前的研究中指出，白色念珠菌感染哺乳類黏膜組織的過程中可分為早期病原菌貼附、中期菌絲侵入、晚期組織損壞等時期。然而，在傳統的老鼠模式動物中，要及時觀察到這些結果是相當困難的。
在先前的實驗中，我們已利用斑馬魚系統研究白色念珠菌感染過程。在本篇研究中，根據斑馬魚組織切片，我們進而驗證白色念珠菌感染斑馬魚的過程與老鼠模式相似，並將其定義為病原菌貼附、菌絲入侵、組織損壞等三個時期。我們接著利用微點陣技術分析在感染過程中，斑馬魚宿主與白色念珠菌的基因表現變化情形。根據分析結果，發現白色念珠菌在感染的過程中會活化與鐵資源搶奪相關的基因表現量，反之在斑馬魚宿主上，則會停止與鐵恆定調控相關的基因表現，根據以上結果，推測鐵資源的競爭在病原與宿主交互作用中應扮演重要角色，亦與白色念珠菌感染過程及致病性有所關連。為驗證此推論，本次實驗藉由給予白色念珠菌額外的鐵離子，來探討鐵對病原菌致病能力的影響。而根據實驗的結果，發現額外的鐵資源與酸性的環境可以明顯延遲白色念珠菌的感染過程，並使得斑馬魚宿主具有較長的存活時間。然而經過進一步的驗證後，發現造成感染延遲的主要原因為鐵離子所導致的酸性環境，而非鐵離子本身所造成的影響。
除了探討病原宿主間的資源競爭外，我們也著重在宿主免疫系統如何抵抗真菌性病原菌的感染。由微陣列技術分析的結果指出，宿主的免疫相關基因表現量在感染時有明顯調升的情形。除此之外，我們也發現白色念珠菌可以誘發斑馬魚後天免疫，而此後天免疫反應可幫助斑馬魚抵抗白色念珠菌的二次感染。由此結果，推論此斑馬魚感染模式未來應可應用於人類真菌性疾病之研究與魚類水產養殖疫苗的開發上。

Candida albicans is a major fungal human pathogen, it exists as a commensal organism on the cutaneous and mucosal surfaces of healthy individuals, but in immuno-compromised patients, C. albicans is responsible for a number of life-threatening infections, causing considerable morbidity and mortality. Previous studies of C. albicans pathogenesis have suggested several steps which may lead to mucosal infection, including early adhesion, invasion, and late tissue damage. However, it is difficult to monitor these events in real time in the traditional mouse model system.
In our previous study, we have established a novel zebrafish model for C. albicans infection study. We found C. albicans infection in zebrafish can also be staged into “adhesion’, “invasion”, and “damage”, which are comparable to the findings observed in the mouse model. We then analyzed the dynamic gene expression profiles of C. albicans and zebrafish during pathogen-host interaction. The results indicated that C. albicans activated its iron scavenging function during invasion and damage phases; whereas zebrafish appeared to cease the iron homeostasis function followed by massive hemorrhage toward the damage stage of infection. This suggested iron competition between the zebrafish host and fungal pathogen might be important for the emergence and progression of C. albicans virulence. To verify this, we administrated excessive iron in low pH condition into the microenvironment of the infection site. We observed significant delay in the progression of C. albicans hyphae formation, consequently, zebrafish survival time was prolonged. Nevertheless, we later found the virulence of C. albicans mostly associated with the microenvironmental pH. The addition of iron supplement only has a minor effect in reducing C. albicans’s virulence.
In addition to resource competition, we also examined the host immune responses against the fungal pathogen. From our microarray data, we identified a set of immune related genes that were up-regulated in the zebrafish during C. albicans infection. Furthermore, we found the host adaptive immunity can help zebrafish defense itself from repeated C. albicans infection. Taken together, we showed zebrafish system can be used in studying human fungal infection disease, and might e useful in developing anti- vaccines for commercial fishes in aquaculture.

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