Abstract Farnesol, a 15-carbon, naturally occurring sesquiterpene alcohol, exists widely in plants and Candida albicans. It inhibits the production of the Pseudomonas Quinolone Signal (PQS) and pyocyanin of the opportunistic pathogen Pseudomonas aeruginosa, but the underlying mechanisms remained unknown. In this study, the actions of farnesol on the growth, production of virulence factors (including PQS signals, elastase, pyocyanin, biofilm, and swarming motility), and the transcription of some essential key genes of three Quorum Sensing (QS) systems and other related virulence genes in the P. aeruginosa PAO1 strain were investigated. Moreover, the qRT-PCR and high throughput transcriptome/proteome sequencing techniques were used to differentiate the transcriptomic/proteomic expressions of the PAO1 strain following farnesol exposure. The experimental results showed that farnesol did not inhibit PAO1 growth or affect its elastase production. However, farnesol did suppress the transcription and protein expression of the pqsABCDE and pqsH genes in the strain's pqs QS system and then inhibit the PQS production, while leaving the transcription and protein expression of pqsR in the pqs system, of lasI and lasR in the las QS system, and of rhlI and rhlR in the rhl QS system unaffected. Farnesol also inhibited the expression of some related virulence genes and the production of the related virulence factors. For example, it inhibited the protein expression of key genes in the phenazine biosynthesis pathway, including key genes related to pyocyanin synthesis (phzM, phzS), inhibiting the strain's capacity for biofilm formation. In addition, farnesol enhanced the transcription and protein expression of key genes in the geraniol degradation pathway. Farnesol also stimulated the PAO1 strain with regard to swarming motility. As a result, we concluded that farnesol can suppress the virulence by inactivating the pqs QS system in pathogen P. aeruginosa, which would be significant to develop a kind of effective drug control the virulence and pathogenesis of this bacteria.

中文翻译：

---

法尼醇对铜绿假单胞菌 PAO1 菌株 pqs 群体感应系统中 pqsABCDE 和 pqsH 及相关毒力因子的抑制作用

摘要 Farnesol 是一种 15 碳、天然存在的倍半萜醇，广泛存在于植物和白色念珠菌中。它抑制机会性病原体铜绿假单胞菌的假单胞菌喹诺酮信号 (PQS) 和绿脓素的产生，但其潜在机制仍然未知。在本研究中，法尼醇对毒力因子（包括 PQS 信号、弹性蛋白酶、绿脓素、生物膜和蜂群运动）的生长、产生以及三个群体感应 (QS) 系统的一些重要关键基因的转录的作用以及其他研究了铜绿假单胞菌 PAO1 菌株中的相关毒力基因。此外，qRT-PCR 和高通量转录组/蛋白质组测序技术用于区分法尼醇暴露后 PAO1 菌株的转录组/蛋白质组表达。实验结果表明，法尼醇不抑制PAO1的生长或影响其弹性蛋白酶的产生。然而，法尼醇确实抑制了菌株 pqs QS 系统中 pqsABCDE 和 pqsH 基因的转录和蛋白质表达，然后抑制了 PQS 的产生，同时使 pqsR 在 pqs 系统中、lasI 和 lasR 在 las 中的转录和蛋白质表达QS系统中的rhlI和rhlR在rhl QS系统中不受影响。Farnesol还抑制一些相关毒力基因的表达和相关毒力因子的产生。例如，它抑制吩嗪生物合成途径中关键基因的蛋白质表达，包括与绿脓素合成相关的关键基因（phzM、phzS），从而抑制菌株形成生物膜的能力。此外，法尼醇增强了香叶醇降解途径中关键基因的转录和蛋白质表达。Farnesol 还刺激了 PAO1 菌株的集群运动。因此，我们得出结论，法尼醇可以通过灭活铜绿假单胞菌的 pqs QS 系统来抑制毒力，这对于开发一种有效的药物控制该细菌的毒力和发病机制具有重要意义。