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中药单体补骨脂酚通过靶向群体感应调节蛋白R(PqsR)减轻(病原体名称未给出)的致病性 。

Traditional Chinese Medicine Monomer Bakuchiol Attenuates the Pathogenicity of via Targeting PqsR.

作者信息

Zeng Jing, Ma Xin, Zheng Yu, Liu Dandan, Ning Wanqing, Xiao Wei, Mao Qian, Bai Zhenqing, Mao Renjun, Cheng Juanli, Lin Jinshui

机构信息

Shaanxi Key Laboratory of Research and Utilization of Resource Plants on the Loess Plateau, College of Life Sciences, Yan'an University, Yan'an 716000, China.

State Key Laboratory for Crop Stress Resistance and High-Efficiency Production, Northwest A&F University (NWAFU), Yangling 712100, China.

出版信息

Int J Mol Sci. 2024 Dec 30;26(1):243. doi: 10.3390/ijms26010243.

Abstract

As the antibiotic resistance of pathogens becomes increasingly severe, it is becoming more feasible to use methods that suppress the virulence of pathogens rather than exerting selective pressure on their growth. , a dangerous opportunistic pathogen, infects hosts by producing multiple virulence factors, which are regulated by quorum-sensing (QS) systems, including the systems, systems, and systems. This study used the chromosome transcription fusion reporter model to screen the traditional Chinese medicine monomer library and found that bakuchiol can effectively inhibit the system and related virulence phenotypes of , including the production of virulence factors (pyocyanin, hydrogen cyanide, elastase, and lectin) and motility (swarming, swimming, and twitching motility) without affecting its growth. Subsequently, through genetic complementation analysis, we found that bakuchiol inhibited the function of the transcriptional activation protein PqsR of the system in in a concentration-dependent manner. Furthermore, molecular dynamics simulation study results indicated that bakuchiol can target PqsR of the system, thereby inhibiting the system. Among the amino acids in PqsR, ALA-168 may be a key amino acid residue in the hydrophobic interaction between PqsR protein and bakuchiol. Finally, in vivo experiments demonstrated that bakuchiol attenuated the pathogenicity of to Chinese cabbage () and . In summary, this study suggests that bakuchiol is an effective inhibitor that targets the system of , providing a new strategy for addressing infections.

摘要

随着病原体的抗生素耐药性日益严重,使用抑制病原体毒力而非对其生长施加选择压力的方法变得越来越可行。铜绿假单胞菌是一种危险的机会致病菌,通过产生多种毒力因子感染宿主,这些毒力因子由群体感应(QS)系统调控,包括Las系统、Rhl系统和Pqs系统。本研究利用染色体转录融合报告模型筛选中药单体库,发现补骨脂酚可有效抑制铜绿假单胞菌的Pqs系统及相关毒力表型,包括毒力因子(绿脓菌素、氰化氢、弹性蛋白酶和凝集素)的产生和运动性(群游、游泳和震颤运动),而不影响其生长。随后,通过基因互补分析,我们发现补骨脂酚以浓度依赖的方式抑制铜绿假单胞菌中Pqs系统的转录激活蛋白PqsR的功能。此外,分子动力学模拟研究结果表明,补骨脂酚可靶向Pqs系统的PqsR,从而抑制Pqs系统。在PqsR的氨基酸中,ALA-168可能是PqsR蛋白与补骨脂酚之间疏水相互作用的关键氨基酸残基。最后,体内实验表明,补骨脂酚减弱了铜绿假单胞菌对大白菜和秀丽隐杆线虫的致病性。综上所述,本研究表明补骨脂酚是一种靶向铜绿假单胞菌Pqs系统的有效抑制剂,为解决铜绿假单胞菌感染提供了新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fffc/11719591/418672ba93db/ijms-26-00243-g001.jpg

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