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標題: Genomic Analysis on Plasmid-Borne Quinolone Resistance in Salmonella Clinical Isolates in Taiwan
作者: 陳盈璁
關鍵字: 基礎研究;生物科學類;沙門氏菌;質體攜帶型?諾酮抗藥基因;基因體學
Antimicrobial resistance is a prominent issue and a worldwide problem. In Enterobacteriaceae, resistance toquinolone or fluoroquinolones is commonly chromosomally-encoded through mutations in DNA gyrase andtopoisomerase IV. Plasmid-mediated quinolone resistance (PMQR) has been reported recently with at leastthree resistance mechanisms to date: Qnr, aminoglycoside acetyltransferase AAC(6')-Ib-cr and QepA.These PMQRS not only reduces the susceptibilities to quinolone drugs, but also affect the dynamics ofdevelopment and acquisition of quinolone resistance. We have identified and reported the first qnrS1 inTaiwan. Subsequent genomics analyses on PMQR by our group have demonstrated the mobilization of qnrBamong plasmids by a novel mobile element, ISCR1. Full resistance to quinolone in Salmonella is stillrelatively uncommon but has been increasing in the past years. More and more PMQR are also reported inSalmonella isolates. The present project is proposed to study the emerging PMQR in clinical Salmonellaand their disseminations. We plan to conduct genomics study on the PMQRs identified in Taiwan. Thespecific aims of this grant proposal include: 1. to study the prevalence of PMQR among clinical Salmonellaisolates in Taiwan. 2. to elucidate the transmission of PMQR and the relation with other antimicrobialresistances by performing genomics analyses on the Salmonella PMQR plasmids. 3. to study the expressionof qnr and their effect on Salmonella by assessing the development of topoisomerase/gyrase mutations. Thelong-term goal of this project is to provide knowledge that may be translated into applicablecounter-resistance strategies for fluoroquinolone-resistance to prevent selection of resistance or lower theresistance level during treatment. This project has basic science and clinical significance in providing newinsights on emerging quinolone resistance and the knowledge to fight against infections by these resistantbacteria.

細菌抗藥性是全世界的重要問題。一般來說腸內菌屬對喹諾酮類藥物的抗藥性都以染色體基因的突變為主。質體攜帶型的喹諾酮抗藥性則是近年才被發現,分為Qnr,AAC(6’)-Ib-cr 以及QepA 三種。它們不只可以降低細菌對喹諾酮藥物的藥敏性,還可以間接地影響染色體中前述抗藥突變的發生與累積。我們曾發表了台灣第一個qnrS1。後續我們又發現qnrB 在質體間利用ISCR1 進行轉移的證據。喹諾酮抗藥性在沙門氏菌中目前報導不多,但近年有增加的趨勢。近年也有越來越多的質體攜帶型喹諾酮抗藥基因從沙門氏菌中被發現。我們計畫進行沙門氏菌質體攜帶型喹諾酮抗藥基因的基因體學研究。研究目標包括:一、研究台灣沙門氏菌中質體攜帶型喹諾酮抗藥基因的分布。二、進行喹諾酮抗藥質體的定序分析,探討抗藥基因傳遞的分子機轉,及與其它抗藥基因的關聯。三、研究qnr基因的表現對沙門氏菌喹諾酮抗藥性及其產生抗藥突變的影響。長遠來看,無論是寄託在防止抗藥性產生,或者找尋降低這些抗藥性的方法,我們都希望這個研究能為將來人類處理喹諾酮抗藥性來鋪路。這個研究計畫兼具了基礎與臨床上的重要性,所產生的知識除了有助於我們更瞭解細菌喹諾酮抗藥性,也有助於人類對抗這些致命的感染症。
其他識別: NSC100-2311-B005-001
Appears in Collections:生命科學系所

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