Coulthurst Sarah J, Williamson Neil R, Harris Abigail K P, Spring David R, Salmond George P C
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK.
Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
Microbiology (Reading). 2006 Jul;152(Pt 7):1899-1911. doi: 10.1099/mic.0.28803-0.
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) QS 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.
粘质沙雷氏菌是人类机会性感染的重要病因。许多（但并非全部）菌株会产生灵菌红素，这是一种次生代谢的红色色素抗生素，其生物合成由pig基因簇指导。群体感应（QS）涉及化学信号分子的产生和检测，作为一种响应群体细胞密度来调节基因表达的手段。先前已证明几株粘质沙雷氏菌拥有N-酰基-L-高丝氨酸内酯（aHSL）群体感应系统。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（pig）和调控位点（aHSL QS）引入缺乏相应性状的菌株中的影响。来自粘质沙雷氏菌ATCC 274（Sma 274）的pig基因簇被转移到无色素菌株粘质沙雷氏菌12株（Sma 12）中。在工程菌株中，色素得以表达，并受受体天然调控系统（aHSL QS和luxS）的控制。此外，将aHSL位点从Sma 12转移到非QS的Sma 274导致aHSL控制作用于多种天然性状，包括色素产生。此外，在本研究过程中，对临床菌株Sma 12的群体感应调控子进行了表征，并鉴定了粘质沙雷氏菌中一些新的群体感应调控性状。这些结果对生物合成和群体感应位点的进化与传播具有启示意义，说明了这些性状的遗传模块性、获取的容易程度以及噬菌体作为水平基因转移载体的能力。
