丁香精油具有高效的抗金黄色葡萄球菌活性，但主成分（丁香酚）对细菌毒力因子的抑制机理尚不明确。作为细菌群体感应系统中的重要组成部分，Agr二元信号转导系统在调节金黄色葡萄球菌毒力因子表达方面起到十分关键的作用。我们发现，丁香酚对于细菌胞内的多种激酶都具有显著的抑制作用。据此推测丁香酚可能通过抑制跨膜蛋白Agr C的C末端组氨酸蛋白激酶结构域的活性，而对金黄色葡萄球菌的Agr二元信号传导系统产生影响，并最终抑制毒力因子的表达。本项目拟通过合成镶嵌Agr C蛋白脂质体模型，实现对丁香酚抑制Agr C中C末端组氨酸蛋白激酶结构域的体外研究。通过探究丁香酚作用与C末端组氨酸蛋白激酶结构域失活之间的关联，掌握其对Agr A的磷酸化通路、调节效应器RNA II和RNA III的转录与表达的影响规律，揭示出丁香酚抑制金黄色葡萄球菌毒力因子表达的分子机制。通过本项目的研究能够为生物抗菌剂的开发提供新的靶点。

Clove essential oil possesses high antibacterial activity against Staphylococcus aureus. But the bacterial virulence factor inhibiting mechanism of its main constituent (eugenol) is uncertain. As an important part of bacterial quorum sensing system, Agr two-component signaling system (TCSS) plays a key role for the expression of bacterial virulence factor. In previous studies, we found that eugenol had a remarkable inhibition effect on the intracellular kinase of bacteria. Based on it, we speculate that eugenol may impact on the Agr TCSS via inhibiting the activity of histidine protein kinase domain on Agr C membrane protein (C-terminal). As a result, the expression of bacterial virulence factor is restricted. In this project, we will realize the in vitro study of the inhibition of eugenol on the histidine protein kinase domain of Agr C by establishing an Agr C embedded proteoliposome model. The relation between eugenol treatment and inactivation of histidine protein kinase domain will be explored. Meanwhile, we will study the influence of eugenol treatment on Agr A phosphorylation pathway as well as transcription and expression of RNA. The results will reveal the molecular inhibition mechanism of eugenol on S. aureus virulence factor. This research could provide a new target for the development of bio-antimicrobial agents.