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Disruption of Quorum Sensing in Pseudomonas aeruginosa by Sinapic Acid: Impacts on Biofilm Formation and Virulence
1, 2, 3 , 3 , 1, 2, 4 , * 1, 2, 4
1  LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal
2  ALICE—Associate Laboratory for Innovation in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, s/n, 4200-465 Porto, Portugal
3  CIQUP-IMS—Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Rua do Campo Alegre, 4169-007 Porto, Portugal
4  DEQ—Department of Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, s/n, 4200-465 Porto, Portugal
Academic Editor: Jordi Vila

Abstract:

Background: Quorum sensing (QS) is a bacterial intercellular communication mechanism mediated by extracellular signalling molecules that regulate gene expression. The las system, consisting of LasI and LasR, is a fundamental QS component in Pseudomonas aeruginosa and plays a crucial role in the formation and maintenance of biofilms as well as in the regulation of virulence factors. Phenolic acids such as sinapic acid are plant secondary metabolites that exhibit antibacterial properties and low toxicity. The aim of this study was to evaluate the potential of sinapic acid as inhibitors of the las-QS system in P. aeruginosa, focussing on their effects on biofilm structure and virulence factor production.

Methods: The inhibitory effect of sinapic acid on the las system was evaluated using bioreporter strains and bioluminescence-based assays. The architecture of the biofilm was analysed using optical coherence tomography (OCT), while the production of virulence factors (pyoverdine, pyocyanin, total proteases, lipases, and gelatinases) and motility was analysed by absorbance measurement and plate agar method.

Results: Sinapic acid inhibited las QS activity by 90 % at a concentration of 1000 µg mL-1. The production of N-3-oxododecanoyl-homoserine lactone, the autoinducer of the las system, was reduced by 60 % at a concentration of 6.25 µg mL-1. This phenolic acid significantly disrupted the biofilm architecture and reduced the biofilm thickness from 25 µm to 14 µm. In addition, sinapic acid significantly reduced the production of important virulence factors and impaired bacterial swarming motility.

Conclusion: Sinapic acid demonstrated strong inhibitory effect on the las QS system, leading to a disruption of the biofilm structure and reduced virulence of P. aeruginosa. These findings support their potential as antipathogenic and antivirulence agents for the treatment of biofilm-associated infections.

Keywords: Antivirulence; biofilm architecture; quorum sensing inhibition; Pseudomonas aeruginosa; sinapic acid.
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