白色念珠菌為人體中最致命的真菌病原菌之一，每年有高達四十萬人遭受白色念珠菌的系統性感染，而此類感染可造成高達50%的死亡率。相較於細菌，針對白色念珠菌致病機制的研究仍極為不足。為了在臨床上發展更好的治療策略，並且幫助新型抗真菌藥物的開發，全面了解白色念珠菌致病機制極為重要。根據其他研究，抗氧化能力和白色念珠菌的致病能力息息相關。例如在白色念珠菌感染人體及治療的過程中，免疫細胞 (例如:巨噬細胞與嗜中性球)及某些抗真菌藥物會藉由產生自由基達到殺菌的效果。因此，白色念珠菌的抗氧化能力對菌體是否能在免疫系統和藥物的治療下存活扮演關鍵性角色。本篇研究主要在於探討轉錄因子Sfp1之作用，發現Sfp1對於白色念珠菌的抗氧化能力具有顯著的調控關係。將SFP1基因剃除後會提升菌株負責傳遞氧化壓力訊號的Hog1激酶的磷酸化程度，並且使另一轉錄因子Cap1的基因表現量增加。此外，將SFP1基因剃除後可顯著提升抗氧化基因的表現量、總抗氧化能力、SOD酵素及麩胱甘肽(glutathione)系統的活性。由於許多抗真菌藥物利用產生自由基達到殺菌功能，此篇研究也進一步探討Sfp1是否和抗藥性有所關聯。綜合以上，本研究提出前所未知的抗氧化能力調控因子，並進一步了解白色念珠菌的抗氧化機制。

Candida albicans is a pathogenic yeast that normally inhabits at skin and mucosa. Due to the limited classes of antifungal drugs available, and the increasing numbers of immunocompromised population, C. albicans has become one of the most prevalent infectious fungi in humans with high mortality rates. During infection process and therapeutics, C. albicans encounters the immune cells and antifungal drugs. Many of them can produce reactive oxygen species (ROS) to kill C. albicans. Therefore, antioxidative capacity is important for survival and pathogenesis of C. albicans. In this study, we characterized the zinc finger transcription factor Sfp1 in the oxidative stress response of C. albicans. The sfp1-deleted mutant possesses active oxidative stress response with a high CAP1 expression and phosphorylated Hog1. Moreover, the sfp1-deleted mutant exhibits high expression levels of antioxidant genes in response to oxidative stresses. Noticeably, the sfp1-deleted mutant also shows a higher total antioxidant capacity, glutathione content, glutathione peroxidase and Sod enzyme activity compared to wild type. In addition, the sfp1-deleted mutant is resistant to ROS-generating antifungal drugs and has lower ROS accumulation upon the treatment, implying that Sfp1 also plays important roles in antifungal drug resistance. Together, our findings provide a previously unknown mechanism for C. albicans antioxidative activity and allow us to further understand the complex regulatory machinery in the context of infection and therapeutics.

Chapter 1. Introduction...7
Chapter 2. Materials and Methods...20
Chapter 3. Results...32
Chapter 4. Discussion...48
Chapter 5. Future perspective...56
Chapter 6. References...58

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