Vocational School of Health Services, Süleyman Demirel University, Isparta, Turkey.
Deparment of Chemistry, Boğaziçi University, Istanbul, Turkey.
J Appl Microbiol. 2018 Sep;125(3):731-739. doi: 10.1111/jam.13892. Epub 2018 Jun 26.
Quorum sensing (QS) is a cell-cell communication system used by a broad spectrum of pathogenic bacteria to control the expression of their virulence genes. The interruption of QS systems of pathogenic bacteria has been considered as a novel way to fight bacterial diseases. In this study, trans-anethole, the main component of anise (Pimpinella anisum) oil was examined for its QS inhibitor (QSI) potential in an attempt to identify novel QSI compound effective against opportunistic pathogen Pseudomonas aeruginosa.
The preliminary screening of QSI capacity of trans-anethole was determined using a quorum-sensing inhibitor screen (QSIS) assay. The QSIS assay indicated that trans-anethole has QSI properties. QSI capacity of trans-anethole was further confirmed by lasB-gfp fussion assay and virulence factor assays. A sub-MIC of trans-anethole reduced the expression of lasB by 57%, elastase production by 59%, protease production by 56%, pyocyanin production by 95% and swarming motility by 68% without inhibiting growth of Pseudomonas aeruginosa PA01. Molecular docking and protein-ligand interaction studies were performed to understand the molecular mechanism underlying inhibitory activity of trans-anethole. The results of these analysis suggested that trans-anethole fits within the binding site of the LasR protein of P. aeruginosa.
Trans-anethole has the potential to inhibit QS-regulated virulence factors in P. aeruginosa by binding to LasR protein, similar to its natural ligand N-(3-oxododecanoyl)-l-homoserine lactone.
In this study, for the first time, it was demonstrated that trans-anethole has the potential to disrupt bacterial communication and can be developed as a novel QSI to combat with P. aeruginosa and other clinically significant pathogens.
群体感应(QS)是一种广泛存在于致病性细菌中的细胞间通讯系统,用于控制其毒力基因的表达。干扰致病菌的 QS 系统被认为是一种防治细菌病的新方法。本研究以茴香油的主要成分反式-茴香脑为研究对象,考察其作为一种新型 QS 抑制剂(QSI)对机会致病菌铜绿假单胞菌的抑制作用。
采用群体感应抑制筛选(QSIS)试验初步筛选反式-茴香脑的 QSI 能力。QSIS 试验表明反式-茴香脑具有 QSI 特性。反式-茴香脑的 QSI 能力进一步通过 lasB-gfp 融合试验和毒力因子试验得到证实。亚 MIC 的反式-茴香脑使 lasB 的表达减少了 57%,弹性蛋白酶的产生减少了 59%,蛋白酶的产生减少了 56%,绿脓菌素的产生减少了 95%,泳动性减少了 68%,而对铜绿假单胞菌 PA01 的生长没有抑制作用。进行分子对接和蛋白-配体相互作用研究以了解反式-茴香脑抑制活性的分子机制。这些分析的结果表明,反式-茴香脑与铜绿假单胞菌的 LasR 蛋白的结合位点相吻合。
反式-茴香脑通过与 LasR 蛋白结合,具有抑制铜绿假单胞菌 QS 调控毒力因子的潜力,与天然配体 N-(3-氧代十二烷酰基)-L-高丝氨酸内酯相似。
本研究首次证明,反式-茴香脑具有破坏细菌通讯的潜力,可开发为新型 QSI,用于对抗铜绿假单胞菌和其他临床重要病原体。