Bio-Organic Chemistry Laboratory, CSIR-National Institute of Oceanography, Dona Paula, Goa, India.
Lett Appl Microbiol. 2013 Mar;56(3):197-207. doi: 10.1111/lam.12034. Epub 2013 Jan 11.
The study aimed to discover quorum sensing (QS) inhibitors from marine sponge-derived actinomycetes and analyse its inhibitory activities against QS-mediated virulence factors in Pseudomonas aeruginosa. Seventy-two actinomycetes isolated from marine invertebrates collected from the western coast of India were screened against the QS indicator strain Chromobacterium violaceum CV12472. Methanol extracts of 12 actinomycetes showing inhibition of violacein production were accessed for downregulation of QS-mediated virulence factors like swarming, biofilm formation, pyocyanin, rhamnolipid and LasA production in Ps. aeruginosa ATCC 27853. The isolates NIO 10068, NIO 10058 and NIO 10090 exhibited very good anti-QS activity, with NIO 10068 being the most promising one. Mass spectrometric analysis of NIO 10068 methanol extract revealed the presence of cinnamic acid and linear dipeptides proline-glycine and N-amido-α-proline in the active extract. Detailed investigation suggested that although linear dipeptide Pro-Gly is to some extent responsible for the observed biological activity, cinnamic acid seems to be the main compound responsible for it. Marine-derived actinomycetes are a potential storehouse for QS inhibitors.
This is the first report not only on marine sponge-associated Streptomyces for anti-QS in Ps. aeruginosa but also on cinnamic acid and proline-derived linear dipeptides proline-glycine as QS inhibitors. The results reveal that marine-derived actinomycetes may not only play a role in the defensive mechanism of their host but also lead to new molecules useful in the development of novel antivirulence drugs.
本研究旨在从海洋海绵衍生放线菌中发现群体感应 (QS) 抑制剂,并分析其对铜绿假单胞菌 QS 介导的毒力因子的抑制活性。从印度西海岸采集的海洋无脊椎动物中分离出 72 株放线菌,用 QS 指示剂菌株 Chromobacterium violaceum CV12472 进行筛选。对显示抑制紫色素产生的 12 株放线菌的甲醇提取物进行评估,以下调铜绿假单胞菌 ATCC 27853 中 QS 介导的毒力因子,如群集、生物膜形成、绿脓菌素、鼠李糖脂和 LasA 的产生。分离株 NIO 10068、NIO 10058 和 NIO 10090 表现出非常好的抗 QS 活性,其中 NIO 10068 最有前途。NIO 10068 甲醇提取物的质谱分析显示,活性提取物中存在肉桂酸和线性二肽脯氨酸-甘氨酸和 N-酰胺-α-脯氨酸。详细的研究表明,尽管线性二肽 Pro-Gly 在某种程度上负责观察到的生物活性,但肉桂酸似乎是负责这种活性的主要化合物。海洋衍生放线菌是 QS 抑制剂的潜在来源。
这不仅是第一个关于海绵相关链霉菌对铜绿假单胞菌的抗 QS 作用的报告,也是第一个关于肉桂酸和脯氨酸衍生的线性二肽脯氨酸-甘氨酸作为 QS 抑制剂的报告。结果表明,海洋衍生放线菌不仅可能在宿主的防御机制中发挥作用,而且可能导致新的分子,这些分子可用于开发新的抗毒力药物。