Center for Microbial Biotechnology, Department of Systems Biology, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.
Department of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, DK-1870 Frederiksberg C, Denmark.
Mar Drugs. 2011 Dec;9(12):2537-2552. doi: 10.3390/md9122537. Epub 2011 Dec 7.
During a global research expedition, more than five hundred marine bacterial strains capable of inhibiting the growth of pathogenic bacteria were collected. The purpose of the present study was to determine if these marine bacteria are also a source of compounds that interfere with the agr quorum sensing system that controls virulence gene expression in Staphylococcus aureus. Using a gene reporter fusion bioassay, we recorded agr interference as enhanced expression of spa, encoding Protein A, concomitantly with reduced expression of hla, encoding α-hemolysin, and rnaIII encoding RNAIII, the effector molecule of agr. A marine Photobacterium produced compounds interfering with agr in S. aureus strain 8325-4, and bioassay-guided fractionation of crude extracts led to the isolation of two novel cyclodepsipeptides, designated solonamide A and B. Northern blot analysis confirmed the agr interfering activity of pure solonamides in both S. aureus strain 8325-4 and the highly virulent, community-acquired strain USA300 (CA-MRSA). To our knowledge, this is the first report of inhibitors of the agr system by a marine bacterium.
在一次全球研究探险中，共收集了五百多株能够抑制致病菌生长的海洋细菌菌株。本研究的目的是确定这些海洋细菌是否也是干扰金黄色葡萄球菌毒力基因表达的agr 群体感应系统的化合物的来源。我们使用基因报告融合生物测定法，记录了 agr 的干扰，即编码蛋白 A 的 spa 的表达增强，同时编码α-溶血素的 hla 和 agr 的效应分子 RNAIII 的表达降低。海洋发光杆菌产生的化合物可干扰金黄色葡萄球菌 8325-4 株的 agr，生物测定指导的粗提物的分步分离导致了两种新型环二肽的分离，分别命名为索罗那肽 A 和 B。Northern blot 分析证实了纯索罗那肽在金黄色葡萄球菌 8325-4 株和高毒力、社区获得性菌株 USA300（CA-MRSA）中的 agr 干扰活性。据我们所知，这是海洋细菌对 agr 系统抑制剂的首次报道。
