School of Biomedical Sciences, Ulster University, Coleraine, BT52 1SA, UK.
Department of Biology, University of York, Wentworth, York, YO10 5DD, UK.
Appl Microbiol Biotechnol. 2019 Apr;103(8):3521-3535. doi: 10.1007/s00253-019-09618-0. Epub 2019 Mar 9.
At present, anti-virulence drugs are being considered as potential therapeutic alternatives and/or adjuvants to currently failing antibiotics. These drugs do not kill bacteria but inhibit virulence factors essential for establishing infection and pathogenesis through targeting non-essential metabolic pathways reducing the selective pressure to develop resistance. We investigated the effect of naturally isolated plant compounds on the repression of the quorum sensing (QS) system which is linked to virulence/pathogenicity in Pseudomonas aeruginosa. Our results show that trans-cinnamaldehyde (CA) and salicylic acid (SA) significantly inhibit expression of QS regulatory and virulence genes in P. aeruginosa PAO1 at sub-inhibitory levels without any bactericidal effect. CA effectively downregulated both the las and rhl QS systems with lasI and lasR levels inhibited by 13- and 7-fold respectively compared to 3- and 2-fold reductions with SA treatment, during the stationary growth phase. The QS inhibitors (QSI) also reduced the production of extracellular virulence factors with CA reducing protease, elastase and pyocyanin by 65%, 22% and 32%, respectively. The QSIs significantly reduced biofilm formation and concomitantly with repressed rhamnolipid gene expression, only trace amount of extracellular rhamnolipids were detected. The QSIs did not completely inhibit virulence factor expression and production but their administration significantly lowered the virulence phenotypes at both the transcriptional and extracellular levels. This study shows the significant inhibitory effect of natural plant-derived compounds on the repression of QS systems in P. aeruginosa.
目前，抗毒药物被认为是潜在的治疗替代品和/或辅助药物，可用于治疗目前失效的抗生素。这些药物不会杀死细菌，但通过靶向非必需代谢途径来抑制建立感染和发病机制所必需的毒力因子，从而减少产生耐药性的选择性压力。我们研究了天然分离的植物化合物对群体感应（QS）系统的抑制作用，该系统与铜绿假单胞菌的毒力/致病性有关。我们的结果表明，肉桂醛（CA）和水杨酸（SA）在亚抑制水平下显著抑制铜绿假单胞菌 PAO1 中 QS 调节和毒力基因的表达，而没有任何杀菌作用。CA 有效地下调了 las 和 rhl QS 系统，lasI 和 lasR 的水平分别比 SA 处理时降低了 13 倍和 7 倍，而 lasI 和 lasR 的水平分别降低了 3 倍和 2 倍。QS 抑制剂（QSI）还降低了细胞外毒力因子的产生，CA 分别使蛋白酶、弹性蛋白酶和绿脓菌素的产量减少了 65%、22%和 32%。QSIs 显著降低了生物膜的形成，同时伴随着 rhamnolipid 基因表达的抑制，仅检测到痕量的细胞外 rhamnolipids。QSIs 并没有完全抑制毒力因子的表达和产生，但它们的给药显著降低了转录和细胞外水平的毒力表型。本研究表明，天然植物衍生化合物对铜绿假单胞菌 QS 系统的抑制具有显著的抑制作用。
