Soni Divya, Smoum Reem, Breuer Aviva, Mechoulam Raphael, Steinberg Doron
Biofilm Research Laboratory, Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel.
Institute for Drug Research, Faculty of Medicine, Hebrew University, Jerusalem, Israel.
BMC Microbiol. 2015 Aug 12;15:159. doi: 10.1186/s12866-015-0499-0.
Bacterial populations communicate through the cell density-dependent mechanism of quorum sensing (QS). Vibrio harveyi, one of the best studied model organisms for QS, was used to explore effects of the synthetic cannabinoid HU-210 on QS and different QS-regulated physiological processes in bacteria.
Analysis of QS-regulated bioluminescence in wild-type and mutant strains of V. harveyi revealed that HU-210 affects the autoinducer-2 (AI-2) pathway, one of three known QS cascades of V. harveyi. Furthermore, QS-mediated biofilm formation and swimming motility in the mutant strain BB152 (AI-1(-), AI-2(+)) were significantly reduced in the presence of HU-210. HU-210 inhibited QS-mediated virulence factor production without any inhibitory effect on bacterial growth. It also alters the expression of several genes, which are regulated by QS, specifically downregulating the genes of the AI-2 QS cascade.
First evidence is being provided for interference of bacterial signal-transduction systems by a synthetic cannabinoid. The effect of HU-210 was specific to the AI-2 cascade in V. harveyi. AI-2 is known as a "universal autoinducer" and interference with its activity opens a broad spectrum of applications for synthetic cannabinoids in future research as a potential anti-QS agent.
细菌群体通过群体感应(QS)的细胞密度依赖性机制进行通讯。哈维氏弧菌是研究QS的最佳模式生物之一,被用于探究合成大麻素HU - 210对细菌中QS及不同QS调控的生理过程的影响。
对哈维氏弧菌野生型和突变株中QS调控的生物发光进行分析发现,HU - 210影响哈维氏弧菌已知的三种QS级联之一的自诱导物-2(AI - 2)途径。此外,在HU - 210存在的情况下,突变株BB152(AI - 1(-),AI - 2(+))中QS介导的生物膜形成和游动性显著降低。HU - 210抑制QS介导的毒力因子产生,而对细菌生长没有任何抑制作用。它还改变了几个受QS调控的基因的表达,特别是下调了AI - 2 QS级联的基因。
首次提供了合成大麻素干扰细菌信号转导系统的证据。HU - 210的作用对哈维氏弧菌中的AI - 2级联具有特异性。AI - 2被称为“通用自诱导物”,对其活性的干扰为合成大麻素在未来研究中作为潜在的抗QS剂开辟了广泛的应用前景。