Sharma Bharti, Chadha Jatin, Khullar Lavanya, Rashpa Simran, Harjai Kusum
Department of Microbiology, Panjab University, Chandigarh, India.
Department of Microbiology, Panjab University, Chandigarh, India.
Microb Pathog. 2025 Sep;206:107781. doi: 10.1016/j.micpath.2025.107781. Epub 2025 Jun 3.
The rise of multidrug-resistant (MDR) Pseudomonas aeruginosa remains an unresolved and substantial challenge to public health, which highlights an urgent need for newer therapeutic strategies. Despite the availability of innumerable antibiotics that effectively eliminate bacterial infections, their unregulated consumption and overexploitation has promoted the development of multidrug resistance by inducing selection pressure. As the world progresses into the post-antibiotic era, antivirulence therapies that exploit a 'disarm-don't kill approach' are gaining momentum as a promising alternative to existing antimicrobial regimens. In view of extensive research being conducted to explore alternate intervention strategies against P. aeruginosa, this review augments scientific literature on repurposing of Food and Drug Administration (FDA)-approved drugs as antivirulence agents, focusing on their ability to disarm quorum sensing (QS), suppress virulence factor production, and disrupt biofilm formation. Drugs from various categories, including but not limited to antifungals, antidiabetics, antihypertensives, antiparasitics, NSAIDs, and antibiotics have been reported to override QS circuitry and QS-regulated virulence pathways in P. aeruginosa through in vitro and in vivo studies. Further, pre-clinical studies with FDA-approved drugs have been substantiated by in silico analysis predicting strong binding affinities to key QS receptors of P. aeruginosa such as LasR, RhlR, and PqsR, underscoring their potential mechanisms of action. Besides, with the well-documented safety profiles, pharmacokinetics, and clinical efficacy of the existing drugs, this repurposing approach streamlines the drug development process, minimizes costs, and accelerates the transition to clinical application. This review underscores the transformative potential of drug repurposing as a cost-effective and sustainable solution to the escalating antimicrobial resistance crisis and advocates for further research to optimize and clinically validate these promising antivirulence therapies.
多重耐药铜绿假单胞菌的出现仍然是公共卫生领域一个尚未解决的重大挑战,这凸显了对更新治疗策略的迫切需求。尽管有无数能有效消除细菌感染的抗生素,但它们的无节制使用和过度开发通过诱导选择压力促进了多重耐药性的发展。随着世界步入后抗生素时代,采用“解除武装而非杀灭方法”的抗毒力疗法作为现有抗菌方案的一种有前景的替代方案正日益受到关注。鉴于正在进行广泛研究以探索针对铜绿假单胞菌的替代干预策略,本综述扩充了关于将美国食品药品监督管理局(FDA)批准的药物重新用作抗毒力剂的科学文献,重点关注它们解除群体感应(QS)、抑制毒力因子产生以及破坏生物膜形成的能力。通过体外和体内研究,已报道包括但不限于抗真菌药、抗糖尿病药、抗高血压药、抗寄生虫药、非甾体抗炎药和抗生素等各类药物可超越铜绿假单胞菌中的QS电路和QS调节的毒力途径。此外,对FDA批准药物的临床前研究已得到计算机模拟分析的证实,该分析预测这些药物与铜绿假单胞菌的关键QS受体如LasR、RhlR和PqsR具有很强的结合亲和力,强调了它们潜在的作用机制。此外,鉴于现有药物有充分记录的安全性、药代动力学和临床疗效,这种重新利用药物的方法简化了药物开发过程,降低了成本,并加速了向临床应用的转化。本综述强调了药物重新利用作为应对不断升级的抗菌药物耐药性危机的一种经济有效且可持续的解决方案的变革潜力,并倡导进一步研究以优化和临床验证这些有前景的抗毒力疗法。