<b>异甘草素作为群体感应抑制剂可减弱铜绿假单胞菌的毒力和致病性。</b>

这项研究表明，查尔酮化合物异甘草素 （ILG） 表现出有效的 QS 活性。ILG 下调 QS相关基因 lasR、lasI、rhlR、rhlI、pqsA、pqsR、lasA、rhlA 和 phzA1 的表达，并抑制亚抑制浓度的蛋白酶、弹性蛋白酶、脓脓素和鼠李糖脂等毒力因子的产生。此外，ILG 减弱了与感染和抗生素耐药性相协调的生物膜形成和运动。大白菜、黑腹果蝇和秀丽隐杆线虫感染模型揭示了 ILG 的体内抗致病能力。ILG 与卡那霉素、妥布霉素或阿米卡星的组合显示出协同抗 P。铜绿假单胞菌效应。耐药诱导试验表明，即使在 20 代中，ILG 也没有诱导铜绿假单胞菌的耐药性，而多粘菌素 B 在第 8 代中诱导了铜绿假单胞菌的耐药性。进一步的研究证实，ILG 可以靶向 las、rhl 和 pqs 系统来干扰铜绿假单胞菌的 QS。总的来说，这些结果表明，ILG 作为一种 QS 抑制剂，是单独或与其他抗生素联合减轻铜绿假单胞菌感染的潜在药物。This study demonstrates that the chalcone compound isoliquiritigenin (ILG) exhibits potent quorum sensing (QS) inhibitory activity. ILG downregulates the expression of QS-related genes including lasR, lasI, rhlR, rhlI, pqsA, pqsR, lasA, rhlA, and phzA1, and suppresses the production of virulence factors such as protease, elastase, pyocyanin, and rhamnolipid at subinhibitory concentrations. Furthermore, ILG attenuates biofilm formation and motility associated with infection and antibiotic resistance. Infection models using Chinese cabbage, Drosophila melanogaster, and Caenorhabditis elegans verified the in vivo anti-pathogenic capacity of ILG. Combinations of ILG with kanamycin, tobramycin, or amikacin exhibited synergistic anti-Pseudomonas aeruginosa effects. Resistance induction assays showed that ILG did not induce drug resistance in Pseudomonas aeruginosa even after 20 passages, while polymyxin B induced resistance in Pseudomonas aeruginosa by the 8th passage. Further experiments confirmed that ILG can target the las, rhl, and pqs systems to interfere with the QS of Pseudomonas aeruginosa. Collectively, these results indicate that ILG, as a QS inhibitor, is a promising drug candidate for alleviating Pseudomonas aeruginosa infections either alone or in combination with other antibiotics.