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Two cinnamic acid derivatives as inhibitors of Pseudomonas aeruginosa las and pqs quorum-sensing systems: Impact on biofilm formation and virulence factors

Title
Two cinnamic acid derivatives as inhibitors of Pseudomonas aeruginosa las and pqs quorum-sensing systems: Impact on biofilm formation and virulence factors
Type
Article in International Scientific Journal
Year
2025-05-02
Authors
Anabela Borges
(Author)
FEUP
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Miguel M. Leitão
(Author)
Other
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Ariana S.C. Gonçalves
(Author)
Other
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Fernanda Borges
(Author)
FCUP
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Simões M
(Author)
FEUP
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Journal
Vol. 187 No. 118090
Pages: 1-19
ISSN: 0753-3322
Publisher: Elsevier
Scientific classification
CORDIS: Natural sciences > Biological sciences > Biological engineering
FOS: Medical and Health sciences > Health sciences
Other information
Authenticus ID: P-018-T5N
Abstract (EN): Introduction: Quorum sensing (QS) is a bacterial communication mechanism that regulates gene expression, playing a crucial role in various physiological processes. Interfering with this signalling pathway is a promising strategy to control bacterial pathogenicity and virulence. Objectives: This study evaluated the potential of two cinnamic acid derivatives, ferulic and sinapic acids, to inhibit the las and pqs systems in Pseudomonas aeruginosa. Their effects on biofilm architecture, virulence factor production and bacterial motility were also investigated. Methods: Bioreporter strains and bioluminescence-based assays were used to evaluate the modulation of QS-activity by cinnamic acid-type phenolic acids. In addition, in silico docking analysis was performed to validate the binding interactions of the cinnamic acid derivatives with QS-receptors. The biofilm architecture was analysed by optical coherence tomography, and virulence factors production (pyoverdine, pyocyanin, total proteases, lipases, gelatinases and siderophores) and motility were measured by absorbance measurement and plate agar method. Results: Ferulic and sinapic acids at 1000 µg mL¿1 inhibited the las and pqs systems by 90 % and 80 %, respectively. The N-3-oxododecanoyl-homoserine lactone production was reduced by 70 % (6.25 µg mL-¹). In silico analysis demonstrated that cinnamic acid derivatives exhibited comparable interactions and higher docking scores than reference ligands and inhibitors. Biofilm thickness decreased from 96 µm to 11 µm, and virulence factors and swarming motility were significantly impaired. The comparable anti-QS activity of cinnamic acid derivatives suggests that the additional methoxy group in sinapic acid does not directly contribute to its anti-QS effect. Conclusion: Ferulic and sinapic acids compromised the biofilm architecture and virulence of P. aeruginosa through QS inhibition. © 2025
Language: English
Type (Professor's evaluation): Scientific
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