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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 factorsPublication . Leitão, Miguel M.; Gonçalves, Ariana S.C.; Sousa, Sérgio F; Borges, Fernanda; Simões, Manuel; Borges, AnabelaIntroduction: 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.
- Interlaboratory Validation of the Cell Transformation Assay (CTA) for Carcinogenic Assessment of BPA AlternativesPublication . El Yamani, N.; Aimonen, K.; Dusinska, M.; Guichard, Y.; Honza, T.; Louro, H.; Pereira, M.J.; Rundén-Pran, E.; SenGupta, T.; Tavares, A.M.; Silva, M.J.Bisphenol A (BPA) has long been used in various plastic products, resins and coatings, making human exposure to this chemical inevitable. Due to its harmful health effects, including endocrine disruption, and immunotoxicity, BPA has been increasingly replaced by several alternative compounds. However, there are still significant gaps in research regarding the safety of these BPA alternatives, particularly concerning their potential carcinogenicity. One of the in vitro assays to assess carcinogenic potential of chemicals is the Bhas-42 cell transformation assay (CTA). The assay can detect both genotoxic and non-genotoxic carcinogens It is valuable in identifying potential cancer risks before widespread exposure occurs, contributing to the development of safer chemicals and products, as well as better regulatory standards while adhering to the 3R concept. The EU-Partnership for the Assessment of Risks from Chemicals (PARC) project is addressing these research gaps to enhance the risk assessment of BPA alternatives. BPA and some alternatives, including BPZ, BPE, BPAP, BPA-MAE, BPP, and TCBPA, were selected for evaluation of their carcinogenic potential using the in vitro 2-stage Bhas-42 CTA. A key objective of the project is to validate the CTA as a reliable in vitro method for assessing carcinogenicity. To ensure consistency and accuracy across participating labs, an interlaboratory comparison was initiated and a standardized SOP was developed, including concentration ranges for controls and BPA analogues, in alignment with OECD guidance document. The first results from the protocol harmonization, using the selected controls, were consistent across all participating labs. BPA and its analogues are being tested, and the results are under evaluation. The data generated will contribute to the overall weight of evidence on the hazards posed by these chemicals and, when combined with findings from other endpoints, will provide a solid basis for refining their regulation.