Pseudomonas aeruginosa is the second most emerging multidrug-resistant, opportunistic pathogen after Acinetobacter baumannii that poses a threat in nursing homes, hospitals, and patients who need devices such as ventilators and blood catheters. Its ability to form quorum sensing-regulated virulence factors and biofilm makes it more resistant to top most therapeutic agents such as carbapenems and next-generation antibiotics. In the current study, we studied the quorum quenching potential of secondary metabolites of Mycoleptodiscus indicus PUTY1 strain. In vitro observation showed a mitigation in virulence factors such as rhamnolipids, protease, elastase pyocyanin, exopolysaccharides, and hydrogen cyanide gas. Furthermore, a significant reduction in the motility such as swimming, swarming, twitching, and inhibition in biofilm formation by Pseudomonas aeruginosa PAO1 was observed. Results of in vitro studies were further confirmed by in silico studies through docking and molecular dynamic simulation of GC-MS-detected compounds of Mycoleptodiscus indicus employing LasR and RhlR proteins. Both in vitro and in silico observations indicate a new alternative approach for combating virulence of Pseudomonas aeruginosa by targeting its protein receptors LasR and RhlR. Graphical abstract.

中文翻译：

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Mycoleptodiscus indicus PUTY1对铜绿假单胞菌PAO1群体感应相关毒力因子和生物膜形成的抑制作用

铜绿假单胞菌是继鲍曼不动杆菌之后第二种最常见的多重耐药性机会性病原体，它对疗养院、医院和需要呼吸机和血液导管等设备的患者构成威胁。其形成群体感应调节的毒力因子和生物膜的能力使其对碳青霉烯类和下一代抗生素等顶级治疗剂更具抵抗力。在目前的研究中，我们研究了 Mycoleptodiscus indicus PUTY1 菌株次级代谢物的群体猝灭潜力。体外观察表明，鼠李糖脂、蛋白酶、弹性蛋白酶绿脓素、胞外多糖和氰化氢气体等毒力因子有所减轻。此外，游泳、蜂拥、抽搐、观察到铜绿假单胞菌 PAO1 对生物膜形成的抑制作用。通过对接和分子动力学模拟的 GC-MS 检测到的采用 LasR 和 RhlR 蛋白的 Mycoleptodiscus indicus 化合物的计算机模拟研究进一步证实了体外研究的结果。体外和计算机中的观察都表明了一种通过靶向其蛋白质受体 LasR 和 RhlR 来对抗铜绿假单胞菌毒力的新替代方法。图形概要。体外和计算机中的观察都表明了一种通过靶向其蛋白质受体 LasR 和 RhlR 来对抗铜绿假单胞菌毒力的新替代方法。图形概要。体外和计算机中的观察都表明了一种通过靶向其蛋白质受体 LasR 和 RhlR 来对抗铜绿假单胞菌毒力的新替代方法。图形概要。