白色念珠菌致病基因FTR1啟動子調控區域之分析研究

• Main Authors: Huang, Szu-Hsuan, 黃思璇
• Other Authors: Lan, Chung-Yu
• Format: Others
• Language: en_US
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/06737803613758086649

碩士 === 國立清華大學 === 分子與細胞生物研究所 === 98 === Abstract Candida albicans is the most common fungus in humans. It can become a pathogen and cause systemic infection in immunocompromised persons. Iron is an essential nutrient for almost every organism. However, free iron is highly limiting within the host. In order to acquire iron and survive under such an iron-restricted condition, C. albicans must compete with their host and other microorganisms. Moreover, previous studies have demonstrated that possession of specialized iron-uptake systems of C. albicans and some of them are related to its virulence. One is the FTR1 gene, which encodes a transmembrane high-affinity iron permease; cells lacking of FTR1 attenuate C. albicans virulence in a mouse model of systemic infection. Interestingly, the expression of FTR1 gene is highly induced under iron-limited environment. However, the molecular mechanism of FTR1 gene regulation in response to iron availability is mostly unknown. In this work, the main focus is to dissect the cis-regulatory elements and trans-factors that are involved in FTR1 gene regulation. Two cis-regulatory elements, IRE1 and IRE2, were revealed in the upstream promoter region of FTR1 and they were responsible for FTR1 gene activation at the low-iron condition. Using computational analysis, NRE and CCAAT box were found to exist within the IRE1 and IRE2 elements. EMSA and site-directed mutagenesis were undertaken to demonstrate that CCAAT-binding factors (CBF) and Nrg1 can directly bind to the regulatory sequences of FTR1 promoter under the low-iron condition. Taken together, this work provides important insight into regulation of C. albicans virulence-related gene in response to the host environment.