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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

2025-06-02Artigo científico Acesso aberto
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dc.contributor.authorLeitão, Miguel M.
dc.contributor.authorGonçalves, Ariana S.C.
dc.contributor.authorSousa, Sérgio F
dc.contributor.authorBorges, Fernanda
dc.contributor.authorSimões, Manuel
dc.contributor.authorBorges, Anabela
dc.date.accessioned2026-02-23T12:29:09Z
dc.date.available2026-02-23T12:29:09Z
dc.date.issued2025-06-02
dc.description.abstractIntroduction: 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.eng
dc.description.abstractHighlights: - Ferulic and sinapic acids inhibit the QS systems las and pqs in P. aeruginosa. - In silico analyses reveals strong affinity for key receptor pockets. - Ferulic and sinapic acids significantly disrupt biofilm architecture. - Ferulic and sinapic acids impair swarming motility and the production of virulence factors. - Additional methoxy group in sinapic acid does not impair anti-QS activityeng
dc.description.sponsorshipThis work was supported by: Project InnovAntiBiofilm (ref. 101157363) financed by European Commission (Horizon-Widera 2023- Acess-02/Horizon-CSA) and Project MultAntiBiofilm (ref. COMPETE2030-FEDER-00852000; Nº 17121), and LEPABE, UIDB/00511/2020 ((DOI: 10.54499/UIDB/00511/2020)) and UIDP/00511/2020 (DOI: 10.54499/UIDP/00511/2020); ALiCE, LA/P/0045/2020 (DOI: 10.54499/LA/P/0045/2020); CIQUP, UIDB/00081/2020 (DOI:10.54499/UIDB/00081/2020); IMS, LA/P/0056/2020 (DOI:10.54499/LA/P/0056/2020); and LAQV, UIDP/50006/2020 (DOI:10.54499/UIDP/50006/2020), funded by national funds through the FCT/MCTES (PIDDAC; Lisbon, Portugal). Sérgio Sousa thanks the FCT for the financial support of his work contract through the Scientific Employment Stimulus—Individual Call (2020.01423.CEECIND). Miguel M. Leitao and Ariana S.C. Gonçalves acknowledge individual PhD fellowships from FCT (2021.07145.BD and 2022.10913.BD, respectively).
dc.identifier.citationBiomed Pharmacother. 2025 Jun:187:118090. doi: 10.1016/j.biopha.2025.118090. Epub 2025 May 2
dc.identifier.doi10.1016/j.biopha.2025.118090
dc.identifier.issn0753-3322
dc.identifier.pmid40318447
dc.identifier.urihttp://hdl.handle.net/10400.18/10986
dc.language.isoen
dc.peerreviewedyes
dc.publisherElsevier
dc.relationBoosting Sustainable Innovation in Developing New Antibiotic Adjuvants to Control Biofilm Resistance
dc.relationLaboratory for Process Engineering, Environment, Biotechnology and Energy
dc.relationLaboratory for Process Engineering, Environment, Biotechnology and Energy
dc.relationALICE - Associate Laboratory in Chemical Engineering
dc.relationAssociated Laboratory for Green Chemistry - Clean Technologies and Processes
dc.relation.hasversionhttps://www.sciencedirect.com/science/article/pii/S0753332225002847?via%3Dihub
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAntivirulence
dc.subjectBiofilm Architecture
dc.subjectFerulic Acid
dc.subjectPseudomonas aeruginosa
dc.subjectQuorum Sensing Inhibition
dc.subjectSinapic Acid
dc.subjectAgentes Microbianos e Ambiente
dc.titleTwo cinnamic acid derivatives as inhibitors of Pseudomonas aeruginosa las and pqs quorum-sensing systems: Impact on biofilm formation and virulence factorseng
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumber101157363
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oaire.awardTitleBoosting Sustainable Innovation in Developing New Antibiotic Adjuvants to Control Biofilm Resistance
oaire.awardTitleLaboratory for Process Engineering, Environment, Biotechnology and Energy
oaire.awardTitleLaboratory for Process Engineering, Environment, Biotechnology and Energy
oaire.awardTitleALICE - Associate Laboratory in Chemical Engineering
oaire.awardTitleAssociated Laboratory for Green Chemistry - Clean Technologies and Processes
oaire.awardURIhttp://hdl.handle.net/10400.18/10982
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00511%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F00511%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA%2FP%2F0045%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F50006%2F2020/PT
oaire.citation.startPage118090
oaire.citation.titleBiomedicine and Pharmacotherapy
oaire.citation.volume187
oaire.fundingStreamHORIZON Coordination and Support Actions
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
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oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
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