The emergence of multidrug-resistant (MDR) strains is a major health problem worldwide. There is an urgent need for novel strategies to combat bacterial infections caused by MDR strains like Pseudomonas aeruginosa and Acinetobacter baumannii. Quorum sensing (QS) is a critical communication system in bacterial community controlling survival and virulence. The awareness of the importance of QS in bacterial infections has stimulated research to identify QS inhibitors (QSIs) to defeat microbes. In this study, four FDA-approved drugs (besides azithromycin as positive QSI) were tested for potential QS inhibition against clinical A. baumannii isolates and P. aeruginosa (PAO1) standard strain. The inhibitory effect of these drugs on virulence factors of both microbes has been investigated. The studied virulence factors include biofilm formation, twitching and swarming motilities, proteolytic enzyme production, and resistance to oxidative stress. The four tested drugs (erythromycin, levamisole, chloroquine, and propranolol) inhibited QS in Chromobacterium violaceum by 84, 72, 55.1, and 37.3%, respectively. They also significantly inhibited virulence factors in both PAO1 and A. baumannii at sub-inhibitory concentrations. These findings were confirmed by qRT-PCR and mice mortality test, where tested drugs highly repressed the expression of abaI gene and showed significantly improved mice survival rates. In addition, molecular docking studies against AbaI and AbaR proteins of QS system in A. baumannii revealed the potential inhibition of QS by tested drugs. Beside their known activities, the tested drugs could be given new life as QSIs to combat A. baumannii nosocomial infections (alone or in combination with antimicrobials).

多重耐药 (MDR) 菌株的出现是世界范围内的主要健康问题。迫切需要新的策略来对抗由绿脓杆菌和鲍曼不动杆菌等耐多药菌株引起的细菌感染。群体感应 (QS) 是控制生存和毒力的细菌群落中的关键通信系统。对 QS 在细菌感染中的重要性的认识激发了研究，以确定 QS 抑制剂 (QSIs) 以击败微生物。在这项研究中，测试了四种 FDA 批准的药物（阿奇霉素作为阳性 QSI 除外）对临床鲍曼不动杆菌和铜绿假单胞菌的潜在 QS 抑制作用(PAO1) 标准菌株。已经研究了这些药物对两种微生物的毒力因子的抑制作用。研究的毒力因素包括生物膜形成、抽搐和蜂群运动、蛋白水解酶的产生和对氧化应激的抵抗力。四种测试药物（红霉素、左旋咪唑、氯喹和普萘洛尔）分别抑制84%、72%、55.1% 和 37.3%的紫色色杆菌中的 QS。它们还在亚抑制浓度下显着抑制 PAO1 和鲍曼不动杆菌中的毒力因子。这些发现通过 qRT-PCR 和小鼠死亡率测试得到证实，其中测试的药物高度抑制abaI的表达基因并显示出显着提高的小鼠存活率。此外，针对鲍曼不动杆菌QS系统的AbaI和AbaR蛋白的分子对接研究揭示了受试药物对QS的潜在抑制作用。除了已知的活性之外，测试的药物还可以作为 QSI 获得新的生命，以对抗鲍曼不动杆菌医院感染（单独或与抗微生物药物联合使用）。