Targeted Inhibition of PqsR in Pseudomonas Aeruginosa PAO1 Quorum-sensing Network by Chalcones As Promising Antibacterial Compounds

Overview

Journal Mol Biol Rep

Date 2025 Jan 30

PMID 39883336

Authors

Negin Arami

Amineh Sadat Tajani

Maryam Hashemi

Tahoura Rezaei

Razieh Ghodsi

Vahid Soheili

Bibi Sedigheh Fazly Bazzaz

Affiliations

Soon will be listed here.

Abstract

Background: Pseudomonas aeruginosa's inherent and adapted resistance makes this pathogen a serious problem for antimicrobial treatments. Furthermore, its biofilm formation ability is the most critical armor against antimicrobial therapy, and the virulence factors, on the other hand, contribute to fatal infection and other recalcitrant phenotypic characteristics. These capabilities are harmonized through cell-cell communication called Quorum Sensing (QS), which results in gene expression regulation via three major interconnected circuits: las, rhl, and pqs system. Pqs circuit specificity in P. aeruginosa made this system an attractive target for antipseudomonal therapy. The current study focuses on novel chalcone derivatives that attenuate P. aeruginosa's pathogenicity by inhibiting the QS system. Chalcones are included in the flavonoid class of phenolic compounds. This family forms one of the greatest groups of bioactive natural products.

Method: The chalcone derivatives's potential activity against the QS system was evaluated through biofilm inhibition, decreased virulence factors production, and gene expression.

Results: Among all the tested compounds, 5H and NMe chalcone derivatives reduced biofilm formation by 60.9% and 78.9%, respectively, and virulence factors production, including pyocyanin (decreased by 5H 30.9% and NMe2 30.7%) and pyoverdine (decreased by 5H 47.1% and NMe2 56.9%) and the QS gene expression (LasR, RhlR, and PqsR) more effectively than other derivatives.

Conclusion: These chalcone compounds can be used as a supplement besides antimicrobial chemotherapy to attenuate pseudomonas pathogenicity.

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