Metabolic and regulatory engineering of Serratia marcescens:: mimicking phage-mediated horizontal acquisition of antibiotic biosynthesis and quorum sensing capacities
Metabolic and regulatory engineering of Serratia marcescens:: mimicking phage-mediated horizontal acquisition of antibiotic biosynthesis and quorum sensing capacities
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DOI：
10.1099/mic.0.28803-0
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发表时间：
2006-07-01
期刊：
影响因子：
2.8
通讯作者：
Salmond, George P. C.
中科院分区：
文献类型：
--
作者：
Coulthurst, Sarah J.;Williamson, Neil R.;Salmond, George P. C.
粘质沙雷氏菌是人类机会性感染的重要原因。许多但不是所有的菌株都能产生灵菌红素，这是一种次级代谢的红色素抗生素，其生物合成受猪基因簇的指导。群体感应（QS）涉及化学信号分子的产生和检测，作为响应群体细胞密度调节基因表达的手段。几株S.先前已显示粘质杆菌具有N-酰基-L-高丝氨酸内酯（aHSL）OS系统。本研究旨在确定通过噬菌体介导的水平基因转移将生物合成基因簇（猪）和调控位点（aHSL QS）引入缺乏相应性状的菌株的影响。猪群S. marcescens ATCC 274（Sma 274）转移到非色素菌株S. marcescens strain 12（Sma 12）.在工程菌株中，色素被表达并置于受体的天然调节系统（aHSL QS和luxS）的控制下。此外，从Sma 12到非QS Sma 274的aHSL基因座的转移导致对各种天然性状（包括色素产生）施加aHSL控制。此外，在本研究中，对临床株Sma 12的QS调节子进行了表征，并在S.鉴定了粘质虫。这些结果对生物合成和QS位点的进化和传播具有影响，说明了这些性状的遗传模块性和易于获得性，以及作为水平基因转移载体的生物合成的能力。
Serratia marcescens is an important cause of opportunistic human infections. Many, but not all, strains produce prodigiosin, a secondary metabolic, red-pigment antibiotic, the biosynthesis of which is directed by the pig gene cluster. Quorum sensing (QS) involves the production and detection of chemical signal molecules as a means to regulate gene expression in response to population cell density. Several strains of S. marcescens have previously been shown to possess an N-acyl-L-homoserine lactone (aHSL) OS system. This study aimed to determine the impact of introducing, by phage-mediated horizontal gene transfer, a biosynthetic gene cluster (pig) and a regulatory locus (aHSL QS) into strains lacking the respective trait. The pig cluster from S. marcescens ATCC 274 (Sma 274) was transferred to the non-pigmented strain, S. marcescens strain 12 (Sma 12). In the engineered strain, pigment was expressed and brought under the control of the recipient's native regulatory systems (aHSL QS and luxS). Moreover, transfer of the aHSL locus from Sma 12 to the non-QS Sma 274 resulted in the imposition of aHSL control onto a variety of native traits, including pigment production. In addition, during this study, the QS regulon of the clinical strain, Sma 12, was characterized, and some novel QS-regulated traits in S. marcescens were identified. The results have implications for the evolution and dissemination of biosynthetic and QS loci, illustrating the genetic modularity and ease of acquisition of these traits and the capacity of phages to act as vectors for horizontal gene transfer.