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標題: The inhibitor screening of Erm(41) methyltransferase from Mycobacterium abscessus.
作者: 陳志維
Chih-Wei Chen
關鍵字: 分枝桿菌;Mycobacterium abscessus
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快速生長型分枝桿菌(RGM)是普遍存在環境中的微生物能夠引發人類各種不同的感染。近年來因為RGM引起的疾病逐年增加,現在治療的方法主要利用注射型藥物搭配口服大環內酯。但近年研究發現,Mycobacterium abscessus會因為大環內酯誘使病原菌內部erythromycin resistance methyltransferases Erm(41)基因表現,使M. abscessus產生對抗大環內酯的抗藥性。所以本實驗選殖Erm(41)基因到大腸桿菌做蛋白質表現,利用生長曲線實驗確認Erm(41)所表現的蛋白在大腸桿菌具有功能,並且嘗試利用X-Ray結晶學解析結晶結構,同時搭配藥篩選和最小抑菌濃度實驗試圖找出Erm(41)蛋白可能的新抑制劑。本實驗結果將有助於發展一種新的治療M. abscessus感染相關疾病的策略。

Rapidly growing mycobacteria (RGM) are common microorganisms in the environment and will lead to a variety of human infections. In recent years, case number of RGM infectious diseases has increased largely. Injection drug combined with oral macrolide is the current clinical treatment to RGM infection. However, recent studies have found that the pathogen Mycobacterium abscessus overexpresses an erythromycin resistance methyltransferase Erm(41) gene to enhance resistance against treatment with macrolide. In this study, we cloned Erm(41) gene into E. coli and the growth curve experiment demonstrated Erm(41) protein can help E. coli grow under treatment of erythromycin. We purify the Erm(41) protein for structure determination by X-ray crystallography. We also conduct drug screening to find new Erm(41) inhibitors and verify the candidate drugs with the minimum inhibitory concentration test. These results will help us to develop a new treatment to defense RGM infection.
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