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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林晉玄(Ching-Hsuan Lin) | |
dc.contributor.author | Pei-Yu Shih | en |
dc.contributor.author | 石佩玉 | zh_TW |
dc.date.accessioned | 2021-07-11T14:35:03Z | - |
dc.date.available | 2023-07-23 | |
dc.date.copyright | 2018-07-23 | |
dc.date.issued | 2018 | |
dc.date.submitted | 2018-07-12 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77798 | - |
dc.description.abstract | 白色念珠菌 (Candida albicans) 為人體常見的伺機性真菌,可與人體建立共生關係,但人體免疫能力降低時,白色念珠菌會成為病原體感染人類。台灣以及美國的醫療統計結果顯示,白色念珠菌為院內感染比例最高的真菌。由於廣泛使用抗真菌藥物,已經使白色念珠菌的抗藥性菌株數量逐漸上升,因此,開發新的抗真菌劑或治療方式有其重要性。幾丁聚醣 (Chitosan) 為幾丁質 (Chitin) 的衍生物,由於具有高生物相容性與低毒性的特性,並且具有抗真菌的效果,幾丁聚醣被認為有高度潛力成為一種新的抗真菌劑,但其抗真菌機制目前尚未明瞭。本研究藉由突變株庫 (Mutant library) 的方式篩選,希望做為了解其機制的第一步,實驗結果顯示,經幾丁聚醣處理後,白色念珠菌 ada2Δ 對於幾丁聚醣的敏感性相較於野生株大幅增加。由穿透式電子顯微鏡結果顯示,野生株以及 ada2Δ在經幾丁聚醣的處理後,細胞表面明顯被破壞並且呈現不規則的形狀。有趣的是,未經任何處理的 ada2Δ 細胞壁厚度顯著變薄,約僅剩野生株一半的厚度。此外,經幾丁聚醣處理的野生株,其細胞壁也有變薄的趨勢。研究顯示,雖然 ADA2 的存在對於白色念珠菌抵抗幾丁聚醣極為重要,然而 ADA2 基因以及受 Ada2 正向調控且與細胞壁相關的基因 (ALS2、PGA45、ACE2) 表現量會被幾丁聚醣抑制。此外,受 Ada2 正向調控的兩個藥物輸出幫浦的基因 (MDR1、CDR1) 表現量亦會被幾丁聚醣抑制。綜合所有實驗結果,推測幾丁聚醣抗真菌特性的機轉之一,是藉由幾丁聚醣會抑制 ADA2 基因表現量的特性,進而影響 ADA2 下游與細胞壁相關基因以及藥物輸出幫浦基因的表現量,改變白色念珠菌的細胞壁厚度以及其輸出幫浦的功能,使白色念珠菌對抗幾丁聚醣的能力下降,敏感度上升。 | zh_TW |
dc.description.abstract | Candida albicans can establish a commensal relationship with healthy humans, but it can also become a human pathogen. Due to high nosocomial infection rate, the first-line drugs for C. albicans have been widely used, which makes drug-resistant strains gradually increase. Developing a new antifungal drug and therapeutic method is therefore necessary. Chitosan, a deacetylated product of chitin, is considered as a potential therapeutic application in fungal infections because of its excellent biocompatibility, biodegradability, and low toxicity. The biocidal action of chitosan against C. albicans shows a great commercial potential but the exact mechanisms of its antimicrobial activity are still unknown. To dissect its antifungal mechanisms, mutant library screening was performed and ADA2 gene was selected, as the ADA2 deletion strain exhibited more susceptible to chitosan than the wild-type strain. Images of transmission electronic microscopy showed that chitosan-treated cell surfaces of both the wild-type and ada2Δ cells were disrupted and displayed irregular shapes. Interestingly, the ada2Δ strain exhibited a significant thinner cell wall thickness than that of the wild-type strain. Furthermore, decreases in cell wall thickness also happened in the chitosan-treated C. albicans wild-type strain. Although the presence of the ADA2 gene is required for tolerance to chitosan, ADA2 expression and several Ada2-mediated cell wall related genes, including ALS2, PGA45, and ACE2, were significantly inhibited by chitosan. Besides, two drug efflux transporter genes, MDR1 and CDR1, regulated by Ada2 were repressed by chitosan. Taken together, this study demonstrated that one of potential antifungal mechanisms of chitosan is to inhibit ADA2 expression, thereby changing C. albicans cell wall thickness or its structure to against this fungus. | en |
dc.description.provenance | Made available in DSpace on 2021-07-11T14:35:03Z (GMT). No. of bitstreams: 1 ntu-107-R05b22052-1.pdf: 3716785 bytes, checksum: 0b5390ad349e00a9bbc0e7aff6e35117 (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 誌謝 i
中文摘要 ii 英文摘要 iii 目錄 iv 圖目錄 vii 表目錄 viii 前言 1 念珠菌症 (Candidiasis) 1 白色念珠菌 (Candida albicans) 2 白色念珠菌細胞壁結構與重要性 5 抗真菌藥物 (Antifungal drugs) 6 抗藥性菌株 (Drug-resistant strains) 7 幾丁聚醣 (Chitosan) 8 ADA2基因 (Alteration/Deficiency in Activation 2 gene) 9 實驗目的 11 材料與方法 12 培養基與生長條件 12 質體與菌株的構築 13 聚合酶鏈鎖反應 (Polymerase chain reaction, PCR) 14 洋菜膠體電泳 (Agarose gel electrophoresis) 14 DNA 片段回收 14 DNA 接合 (DNA ligation) 15 E. coli 轉型作用 (Transformation) 15 E. coli 質體萃取 (Plasmid extraction) 15 C. albicans 轉型作用 16 生長曲線測量 (Growth curve) 17 敏感性測試 (Sensitivity test) 17 抽取白色念珠菌RNA 17 反轉錄聚合酶鏈式反應 (Reverse Transcription-PCR) 18 定量即時聚合酶鏈鎖反應 (Quantitative real time polymerase chain reaction, qPCR) 19 穿透式電子顯微鏡 (Transmission electron microscopy, TEM) 19 結果 21 鑑定 ada2 突變株 (ada2Δ) 及 ADA2 互補株 (ada2Δ::ADA2) 21 白色念珠菌 ada2 突變株生長比野生株緩慢 22 白色念珠菌 ada2 突變株施加幾丁聚醣後,表現高敏感性 22 幾丁聚醣影響白色念珠菌野生株細胞表面的完整性,並且破壞 ada2 突變株的細胞壁以及細胞膜 23 與野生株 SC5314 相比,ada2 突變株以及經幾丁聚醣處理後的野生株皆有細胞壁變薄的現象 24 相較於野生株,ada2 突變株對於細胞表面結構干擾劑 (Cell surface-disturbing agents) 的敏感度大幅提高。 25 幾丁聚醣抑制 ADA2 基因的表現量 26 細胞壁相關基因 (Cell wall related genes) 受到 Ada2 的正向調控,然而被幾丁聚醣抑制 28 藥物輸出幫浦蛋白基因 (Drug efflux pumps) 受到 Ada2 的正向調控,然而被幾丁聚醣抑制 29 白色念珠菌 ada2 突變株發生細胞聚集現象 30 討論 31 結論 38 未來研究方向 39 圖表 42 參考文獻 58 附錄 71 | |
dc.language.iso | zh-TW | |
dc.title | 白色念珠菌 ADA2 基因的剔除導致細胞壁厚度的改變而增加對幾丁聚醣的感受性 | zh_TW |
dc.title | Deletion of transcription factor Ada2 increases sensitivity to chitosan by altering cell wall thickness in Candida albicans | en |
dc.type | Thesis | |
dc.date.schoolyear | 106-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 羅秀容(Hsiu-Jung Lo),陳進庭(Chin-Tin Chen),呂俊毅(Jun-Yi Leu),張麗冠(Li-Kwan Chang) | |
dc.subject.keyword | 白色念珠菌,幾丁聚醣,Ada2,細胞壁厚度,輸出幫浦, | zh_TW |
dc.subject.keyword | Candida albicans,chitosan,Ada2,cell wall thickness,efflux pump, | en |
dc.relation.page | 77 | |
dc.identifier.doi | 10.6342/NTU201801455 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2018-07-12 | |
dc.contributor.author-college | 生命科學院 | zh_TW |
dc.contributor.author-dept | 生化科技學系 | zh_TW |
dc.date.embargo-lift | 2023-07-23 | - |
顯示於系所單位: | 生化科技學系 |
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