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Identification of natural product compounds as quorum sensing inhibitors in Pseudomonas fluorescens P07 through virtual screening
Bioorganic & Medicinal Chemistry ( IF 3.5 ) Pub Date : 2018-06-30 , DOI: 10.1016/j.bmc.2018.06.039
Ting Ding , Tingting Li , Jianrong Li

Pseudomonas fluorescens, a Gram-negative psychrotrophic bacteria, is the main microorganism causing spoilage of chilled raw milk and aquatic products. Quorum sensing (QS) widely exists in bacteria to monitor their population densities and regulate numerous physiological activities, such as the secretion of siderophores, swarming motility and biofilm formation. Thus, searching for quorum sensing inhibitors (QSIs) may be another promising way to control the deterioration of food caused by P. fluorescens. Here, we screened a traditional Chinese medicine (TCM) database to discover potential QSIs with lesser toxicity. The gene sequences of LuxI- and LuxR-type proteins of P. fluorescens P07 were obtained through whole-genome sequencing. In addition, the protein structures built by homology modelling were used as targets to screen for QSIs. Twenty-one compounds with a dock score greater than 6 were purchased and tested by biosensor strains (Chromobacterium violaceum CV026 and Agrobacterium tumefaciens A136). The results showed that 10 of the compounds were determined as hits (hit rate: 66.67%). Benzyl alcohol, rhodinyl formate and houttuynine were effective QSIs. The impact of the most active compound (benzyl alcohol) on the phenotypes of P. fluorescens P07, including swimming and swarming motility, production of extracellular enzymes and siderophores, N-acylhomoserine lactone (AHLs) content and biofilm formation were determined. The inhibitory mechanism of benzyl alcohol on the QS system of P. fluorescens P07 is further discussed. This study reveals the feasibility of searching for novel QSIs through virtual screening.



中文翻译:

通过虚拟筛选鉴定荧光假单胞菌P07中作为群体感应抑制剂的天然产物化合物

荧光假单胞菌是一种革兰氏阴性精神营养细菌,是导致冷冻生乳和水产品变质的主要微生物。群体感应(QS)广泛存在于细菌中,以监测其种群密度并调节众多生理活动,例如铁载体的分泌,蜂群运动和生物膜形成。因此,寻找群体感应抑制剂(QSI)可能是控制P引起的食物变质的另一种有前途的方法。荧光素。在这里,我们筛选了传统中药(TCM)数据库,以发现毒性较小的潜在QSI。荧光假单胞菌LuxI和LuxR型蛋白的基因序列通过全基因组测序获得P07。此外,通过同源性建模构建的蛋白质结构被用作筛选QSI的目标。购买了21个对接点得分大于6的化合物,并通过生物传感器菌株(Violaceum violaceum CV026和Agrobacterium tumefaciens A136)进行了测试。结果表明,有10种化合物被定为命中率(命中率:66.67%)。苯甲醇,甲酸若丹宁和鱼腥草碱是有效的QSI。活性最高的化合物(苄醇)对P表型的影响。荧光素P07,包括游泳和成群运动,细胞外酶和铁载体的产生,N确定了酰基高丝氨酸内酯(AHLs)的含量和生物膜的形成。苄醇的QS系统上的抑制机制P。进一步讨论了荧光素P07。这项研究揭示了通过虚拟筛选搜索新颖的QSI的可行性。

更新日期:2018-06-30
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