Key Laboratory of Resources Biology and Biotechnology in Western China, Ministry of Education, The College of Life Sciences, Northwest University, Xi'an 710069, China.
Provincial Key Laboratory of Biotechnology of Shaanxi Province, The College of Life Sciences, Northwest University, Xi'an 710069, China.
Int J Mol Sci. 2021 Nov 24;22(23):12699. doi: 10.3390/ijms222312699.
, an important opportunistic pathogen, is capable of producing various virulence factors and forming biofilm that are regulated by quorum sensing (QS). It is known that targeting virulence factor production and biofilm formation instead of exerting selective pressure on growth such as conventional antibiotics can reduce multidrug resistance in bacteria. Therefore, many quorum-sensing inhibitors (QSIs) have been developed to prevent or treat this bacterial infection. In this study, wogonin, as an active ingredient from , was found to be able to inhibit QS system of PAO1. Wogonin downregulated the expression of QS-related genes and reduced the production of many virulence factors, such as elastase, pyocyanin, and proteolytic enzyme. In addition, wogonin decreased the extracellular polysaccharide synthesis and inhibited twitching, swimming, and swarming motilities and biofilm formation. The attenuation of pathogenicity in PAO1 by wogonin application was further validated in vivo by cabbage infection and fruit fly and nematode survival experiments. Further molecular docking analysis, pathogenicity examination of various QS-related mutants, and PQS signal molecule detection revealed that wogonin could interfere with PQS signal molecular synthesis by affecting and . Taken together, the results indicated that wogonin might be used as an anti-QS candidate drug to attenuate the infection caused by .
铜绿假单胞菌是一种重要的机会性病原体,能够产生多种毒力因子并形成生物膜,这些过程受到群体感应(QS)的调控。已知针对毒力因子产生和生物膜形成,而不是对生长施加选择性压力(如传统抗生素),可以减少细菌的多药耐药性。因此,已经开发了许多群体感应抑制剂(QSIs)来预防或治疗这种细菌感染。在这项研究中,发现来自黄芩的活性成分汉黄芩素能够抑制 PAO1 的 QS 系统。汉黄芩素下调了与 QS 相关的基因表达,并减少了许多毒力因子的产生,如弹性蛋白酶、绿脓菌素和蛋白酶。此外,汉黄芩素减少了细胞外多糖的合成,并抑制了菌毛运动、泳动和群集运动以及生物膜的形成。汉黄芩素在白菜感染和果蝇及线虫存活实验中进一步验证了其对 PAO1 致病性的减弱作用。进一步的分子对接分析、各种与 QS 相关的突变体的致病性检查以及 PQS 信号分子的检测表明,汉黄芩素可以通过影响 LasR 和 RhIR 来干扰 PQS 信号分子的合成。总之,这些结果表明,汉黄芩素可能被用作一种抗 QS 候选药物,以减轻铜绿假单胞菌引起的感染。