Department of Biotechnology, School of Life Sciences, Pondicherry University, Puducherry, 605014, India.
Department of Microbiology, School of Life Sciences, Pondicherry University, Puducherry, 605014, India.
Braz J Microbiol. 2020 Jun;51(2):467-487. doi: 10.1007/s42770-020-00235-y. Epub 2020 Feb 21.
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.
铜绿假单胞菌是仅次于鲍曼不动杆菌的第二大新兴的多药耐药性、机会性病原体，它对疗养院、医院以及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药物更具耐药性。在本研究中，我们研究了 Mycoleptodiscus indicus PUTY1 菌株的次级代谢产物的群体感应淬灭潜力。体外观察表明，鼠李糖脂、蛋白酶、弹性蛋白酶、胞外多糖和氰化氢等毒力因子的水平降低。此外，还观察到铜绿假单胞菌 PAO1 的运动性（如游泳、群集、扭动）显著降低，生物膜形成受到抑制。通过使用 LasR 和 RhlR 蛋白对接和对 Mycoleptodiscus indicus 的 GC-MS 检测化合物进行分子动力学模拟，对体外研究结果进行了进一步的计算机模拟验证。体外和计算机模拟观察都表明，通过针对铜绿假单胞菌的蛋白质受体 LasR 和 RhlR 来对抗其毒力是一种新的替代方法。
