Anti-quorum sensing and antibiofilm activity of coumarin derivatives against Pseudomonas aeruginosa PAO1: Insights from in vitro and in silico studies

• Published in: Iranian journal of basic medical sciences Vol. 26; no. 4; pp. 445 - 452
• Main Authors: Tajani, Amineh Sadat, Amiri Tehranizadeh, Zeinab, Pourmohammad, Arianoosh, Pourmohammad, Armin, Iranshahi, Milad, Farhadi, Faegheh, Soheili, Vahid, Fazly Bazzaz, Bibi Sedigheh
• Format: Journal Article
• Language: English
• Published: Iran Mashhad University of Medical Sciences 01.04.2023
• Subjects: biofilm; Biofilms; coumarin; Gene expression; Kinases; microbial resistance; Original; pseudomonas aeruginosa; quorum sensing; Biofilm; Pseudomonas aeruginosa; Microbial resistance; Quorum sensing; Coumarin
• ISSN: 2008-3866; 2008-3874
• DOI: 10.22038/IJBMS.2023.69016.15047

Biofilm-associated infections are challenging to manage or treat since the biofilm matrix is impenetrable to most antibiotics. Therefore, the best approach to deal with biofilm infections is to interrupt the construction during the initial levels. Biofilm formation has been regulated through the quorum sensing (QS) network, making it an attractive target for any antibacterial therapy. Here, some coumarin members, including umbelliprenin, 4-farnesyloxycoumarin, gummosin, samarcandin, farnesifrol A, B, C, and auraptan, have been assessed as QS inhibitors and Their potential inhibitory effects on biofilm formation and virulence factor production of PAO1 were evaluated. First, the interaction of these compounds was investigated against one of the major transcriptional regulator proteins, PqsR, using molecular docking and structural analysis methodology. After that, evaluations indicated that 4-farnesyloxycoumarin and farnesifrol B showed considerable reduction in biofilm formation (62% and 56%, respectively), virulence factor production, and synergistic effects with tobramycin. Moreover, 4-farnesyloxycoumarin significantly (99.5%) reduced gene expression. The biofilm formation test, virulence factors production assays, gene expression analysis, and molecular dynamic simulations data demonstrated that coumarin derivatives are a potential anti-QS family through PqsR inhibition.