菸鹼醯酸於痤瘡丙酸桿菌生物膜之作用

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題名:	菸鹼醯酸於痤瘡丙酸桿菌生物膜之作用 The Effect of Nicotinamide on Biofilm of Cutibacterium acnes
作者:	施怡賢 SHIH, YI-HSIEN
貢獻者:	醫學科學研究所博士班李婉若沈芯伃
關鍵詞:	痤瘡丙酸桿菌;生物膜;菸鹼醯銨;去氧核醣核酸酶;尋常性痤瘡 Cutibacterium acnes;Biofilm;Nicotinamide;Deoxyribonuclease;Acne vulgaris
日期:	2022-01-13
上傳時間:	2022-08-12 09:19:01 (UTC+8)
摘要:	研究動機與目的: 生物膜是一群藉由自身產生的基質包覆而成的細胞社區，它們可能導致慢性感染以及抗生素抗藥性。痤瘡丙酸桿菌(Cutibacterium acnes，舊名稱為Propionibacterium acnes)參與尋常性痤瘡的致病機轉。而尋常性痤瘡病人毛囊中痤瘡丙酸桿菌形成之生物膜，曾被顯示與抗生素易感性降低以及致病性增加有關。因此，發展對抗痤瘡丙酸桿菌生物膜之新對策具有高度需求。過去的臨床研究指出，菸鹼醯胺(nicotinamide)因具有抗發炎特性，可用來做為尋常性痤瘡之輔助治療。然而，菸鹼醯胺對於痤瘡丙酸桿菌生物膜之影響仍不清楚。重要研究方法: 我們以試管內及活體內實驗方法，針對菸鹼醯胺對於痤瘡丙酸桿菌生物膜之影響進行研究。研究結果: 為探討菸鹼醯胺對於痤瘡丙酸桿菌生物膜之影響，我們於試管內進行研究，在痤瘡丙酸桿菌形成生物膜之前與之後添加菸鹼醯胺。結果發現發現菸鹼醯胺可顯著抑制痤瘡丙酸桿菌生物膜形成，亦可加強其分解。另外，我們亦發現菸鹼醯胺不論於試管內或活體內，均明顯提高痤瘡丙酸桿菌對於四環黴素(tetracycline)之易感性。許多微生物之生物膜能被第一型去氧核醣核酸酶有效去除。我們以蛋白質與分子之電腦模擬運算、表面電漿共振分析、以及酵素活性測試發現，菸鹼醯胺(作為輔酶)可能與第一型去氧核醣核酸酶進行交互作用，並活化該酵素。結論: 總結以上，我們相信這份研究將是發展對抗其他皮膚慢性感染生物膜新對策的第一步。 Biofilms are communities of cells enclosed in a self-produced matrix; they contribute to chronic infections and antibiotic resistance. Cutibacterium (C.) acnes (formerly Propioni-bacterium acnes) participates in the pathogenesis of acne vulgaris. Biofilm of C. acnes has been shown to be associated with decreased antimicrobial susceptibility and increased virulence factors in the follicles of acne patients. Thus, developments of new strategies targeting C. acnes biofilm dispersion are highly needed. Previous clinical studies indicated that nicotinamide (NAM), with its anti-inflammatory properties, is an useful adjunctive treatment for acne vulgaris. The influence of NAM on biofilm of C. acnes is still unclear. Our study probes into the effects of NAM on biofilms of C. acnes through in vitro and in vivo methods. To investigate the effects of NAM on biofilm of C. acnes, we added NAM before or after cultivation of biofilm of C. acnes in vitro. Our results showed that NAM significantly inhibited C. acnes biofilm formation and enhanced its degradation. Moreover, we also found that NAM significantly increased the sensitivity of C. acnes to tetracycline treatment in vitro and in vivo. Biofilms of various microbes can effectively be treated with deoxyribonuclease (DNase) I. Using computational protein-ligand docking, surface plasmon resonance analysis, and an enzymatic activity assay, we discovered that NAM, as a coenzyme, could interact and activate DNase I. In conclusion, we believe that our study could be the first step to develop new strategies against biofilms in other chronic cutaneous infections in the future.
描述:	博士指導教授:李婉若共同指導教授:沈芯伃委員:廖怡華委員:王莉芳委員:鍾筱菁委員:李婉若委員:沈芯伃
資料類型:	thesis
顯示於類別:	[醫學科學研究所] 博碩士論文

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