Inhibition of biofilm formation, quorum sensing and virulence factor production in Pseudomonas aeruginosa PAO1 by selected LasR inhibitors

International Microbiology - Tập 26 - Trang 851-868 - 2023
Aishwarya Vetrivel1, Preethi Vetrivel2, Kavitha Dhandapani1, Santhi Natchimuthu1, Monica Ramasamy1, Soundariya Madheswaran1, Rajeswari Murugesan1
1Department of Biochemistry, Biotechnology and Bioinformatics, Avinashilingam Institute for Home Science and Higher Education for Women, Coimbatore, India
2Department of Pharmacy, National University of Singapore, Singapore 119077, Singapore

Tóm tắt

The quorum sensing network of Pseudomonas aeruginosa mediates the regulation of genes controlling biofilm formation and virulence factors. The rise of drug resistance to Pseudomonas aeruginosa infections has made quorum sensing–regulated biofilm formation in clinical settings a major issue. In the present study, LasR inhibitors identified in our previous study were evaluated for their antibiofilm and antiquorum sensing activities against P. aeruginosa PAO1. The compounds selected were (3-[2-(3,4-dimethoxyphenyl)-2-(1H-indol-3-yl)ethyl]-1-(2-fluorophenyl)urea) (C1), (3-(4-fluorophenyl)-2-[(3-methylquinoxalin-2-yl)methylsulfanyl]quinazolin-4-one) (C2) and (2-({4-[4-(2-methoxyphenyl)piperazin-1-yl]pyrimidin-2-yl}sulfanyl)-N-(2,4,6-trimethylphenyl)acetamide) (C3). The minimum inhibitory concentrations of C1 and C2 were 1000 μM, whereas that of C3 was 500 μM. At sub-MICs, the compounds showed potent antibiofilm activity without affecting the growth of P. aeruginosa PAO1. Electron microscopy confirmed the disruption of biofilm by the selected compounds. The antiquorum sensing activity of the compounds was revealed by the inhibition of violacein in Chromobacterium violaceum and the inhibition of swimming and swarming motilities in P. aeruginosa PAO1. Furthermore, the compounds also attenuated the production of quorum sensing–mediated virulence factors. The qRT-PCR revealed the downregulation of quorum sensing regulatory genes, namely lasI, lasR, rhlI, rhlR, lasB, pqsA and pqsR. The selected compounds also exhibited lower cytotoxicity against peripheral blood lymphocytes. Thus, this study could pave a way to explore these compounds for the development of therapeutic agent against Pseudomonas aeruginosa biofilm–related infections.

Tài liệu tham khảo

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