探討白色念珠菌GPH1基因之功能

白色念珠菌（Candida albicans）是一種常見的伺機性真菌病原體，在免疫功能低下的病人中會引起全身性念珠菌病。根據台灣院內感染監視資訊系統（TNIS）監視報告指出，台灣加護病房不論是區域醫院或醫學中心，念珠菌感染的情況都有增加的趨勢，目前主要的菌種以Candida albicans較為常見，而白色念珠菌為人類真菌感染最常見的案例，儘管有抗真菌藥物，侵入性念珠菌病還是具有高死亡率且副作用及抗真菌藥物菌株產生，顯示開發新抗真菌藥物的必要性。白色念珠菌型態轉換能力是毒力特性核心之一，因此持續開發控制白色念珠菌型態發生因子為標靶之藥物實為必須。先前研究顯示CaCDC4透過其連接酶催化菌絲型態正調節受質Sol1泛素化而透過蛋白酶體降解的角色而為菌絲型態的負調控者。然而，CaCDC4 SOL1雙基因剔除菌株仍能維持菌絲生長，促使我們尋找其它CaCdc4的受質。先前實驗室以親和力蛋白質純化法找出與CaCdc4有直接交互作用的相關蛋白質CaGPH1（orf19.7021）並以酵母菌雙雜合檢測法確認。重要的是，我們也證實了持續表現CaGPH1能部分地遏止因CaCDC4表現下降而造成的菌絲生成。 GPH1推定為肝醣磷酸化酶，其Saccharomyces cerevisiae同源基因編碼蛋白具備該功能而與碳水化合物代謝有關，尤其它的活性是分解肝醣所必須且與真菌細胞壁

關鍵字

白色念珠菌；形態生成；芽管；附著；細胞表面疏水性；體外致病力檢測法

並列摘要

Candida albicans is an opportunistic human fungal pathogen that causes systemic candidiasis in immunocompromised patients. The Taiwan Nosocomial Infections Surveillance System (TNIS) surveillance report has indicated that the Taiwan intensive care unit, whether it is a regional hospital or medical center, has a trend of increasing candidiasis, and the most common strain is caused by C. albicans. Indeed, C. albicans is the most common cause of human fungal infections globally, despite the availability of antifungal drugs, the invasive candidiasis has a high mortality in addition to the side effect and occurrence of drug resistant strains. Ability in morphological transition is one of the key features in C. albicans virulence. Hence, it is essential to keep on developing new anti-C. albicans drugs that target factors controlling morphogenesis. The previous study reveals that CaCDC4 participates in the repression in filamentous growth of C. albicans and targets to Sol1, the substrate of a positive regulator of filamentation, for degradation through proteasome by its catalytic activity of E3 ubiquitin ligase. However, the fact that the double CaCDC4 SOL1 deletion strain exhibits filamentous growth prompts us to search for other CaCdc4 substrates. We have previously identified CaGPH1 (orf19.7021) as one of the CaCdc4 associated proteins by affinity purification and verified by the yeast two-hybrid assay. Significantly, we have also shown that constitutively expression CaGPH1 partially suppresses the filamentation due to the repressed expression of CaCDC4 in C. albicans. CaGPH1 gene is a putative glycogen phosphorylase as is Saccharomyces cerevisiae homolog that is known to participate in carbonhydrate metabolism, particularly in glycogen catabolism that is associated with synthesis of

並列關鍵字

Candida albicans ； morphogenesis ； germ tube ； adhesion ； cell surface hydrophobicity ； in vitro virulence assay

參考文獻

Daher, J. Y., Koussa, J., Younes, S., & Khalaf, R. A. (2011). The Candida albicans Dse1 Protein Is Essential and Plays a Role in Cell Wall Rigidity, Biofilm Formation, and Virulence. Interdisciplinary Perspectives on Infectious Diseases, 2011. doi:10.1155/2011/504280

陳星宇, 詹明錦, & 孫俊仁. (2012). 侵入性黴菌感染及感染控制. [Invasive Fungal Infection and Infection Control]. 感染控制雜誌, 22(1), 12-20.

Alfatah, M., Bari, V. K., Nahar, A. S., Bijlani, S., & Ganesan, K. (2017). Critical role for CaFEN1 and CaFEN12 of Candida albicans in cell wall integrity and biofilm formation. Scientific Reports, 7, 40281. doi:10.1038/srep40281

Arnaud, M. B., Costanzo, M. C., Skrzypek, M. S., Binkley, G., Lane, C., Miyasato, S. R., & Sherlock, G. (2005). The Candida Genome Database (CGD), a community resource for Candida albicans gene and protein information. Nucleic Acids Res, 33(Database issue), D358-363. doi:10.1093/nar/gki003

Atir-Lande, A., Gildor, T., & Kornitzer, D. (2005). Role for the SCF(CDC4) Ubiquitin Ligase in Candida albicans Morphogenesis. Molecular Biology of the Cell, 16(6), 2772-2785. doi:10.1091/mbc.E05-01-0079

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探討白色念珠菌GPH1基因之功能

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