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<p>Anti-virulence strategies are gaining recognition as promising alternatives for bacterial infection control. They act by suppressing quorum sensing circuits, disrupting biofilm formation, and inhibiting toxin production. However, the emergence of resistant bacterial mutants highlights the need for anti-virulence agents that do not induce resistance. <i>Pseudomonas aeruginosa</i> produces autoinducers like N-acyl-homoserine lactone (AHL), which enhance cell-population and coordinate gene expression. Plant-derived compounds, particularly O-methylated phenolic flavonoids, have shown promise in overcoming antibiotic resistance. Herein, compounds such as formononetin (isoflavone) and 4′-methoxyflavonol (flavonol) possess pharmacological properties beneficial for human health and have been found to inhibit AHL-mediated virulence factors in <i>P. aeruginosa</i>. These flavonoids effectively reduced the production of virulence factors like exopolysaccharides, elastase, protease, pyocyanin, and rhamnolipids assessed by biochemical assays. Motility assays demonstrated a reduction in bacterial movement, and biofilm formation was quantified and visualized using Zeiss Confocal Laser Scanning Microscopy. Gene expression analysis by RT-qPCR revealed that the flavonoids suppressed <i>las</i> and <i>rhl</i> circuits associated with virulence factor synthesis. Among the selected two compounds, 4′-methoxyflavonol exhibited the strongest inhibitory effect against <i>P. aeruginosa</i>. Overall, this study underscores the dual role of dietary phenolic flavonoids in supporting biological functions and serving as natural anti-quorum sensing agents, offering promising strategies to mitigate bacterial virulence.</p>

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Disruption of quorum sensing and biofilm formation in Pseudomonas aeruginosa by plant-based O-methylated flavonoids

  • 期刊论文

  • 发表日期：

    2025年10月30日

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  • Maalavikha Prabhakaran,
  • Mathumitha Prabakaran,
  • Abinaya Kanagaraja,
  • Subash C. B. Gopinath,
  • Pachaiappan Raman

摘要

Anti-virulence strategies are gaining recognition as promising alternatives for bacterial infection control. They act by suppressing quorum sensing circuits, disrupting biofilm formation, and inhibiting toxin production. However, the emergence of resistant bacterial mutants highlights the need for anti-virulence agents that do not induce resistance. Pseudomonas aeruginosa produces autoinducers like N-acyl-homoserine lactone (AHL), which enhance cell-population and coordinate gene expression. Plant-derived compounds, particularly O-methylated phenolic flavonoids, have shown promise in overcoming antibiotic resistance. Herein, compounds such as formononetin (isoflavone) and 4′-methoxyflavonol (flavonol) possess pharmacological properties beneficial for human health and have been found to inhibit AHL-mediated virulence factors in P. aeruginosa. These flavonoids effectively reduced the production of virulence factors like exopolysaccharides, elastase, protease, pyocyanin, and rhamnolipids assessed by biochemical assays. Motility assays demonstrated a reduction in bacterial movement, and biofilm formation was quantified and visualized using Zeiss Confocal Laser Scanning Microscopy. Gene expression analysis by RT-qPCR revealed that the flavonoids suppressed las and rhl circuits associated with virulence factor synthesis. Among the selected two compounds, 4′-methoxyflavonol exhibited the strongest inhibitory effect against P. aeruginosa. Overall, this study underscores the dual role of dietary phenolic flavonoids in supporting biological functions and serving as natural anti-quorum sensing agents, offering promising strategies to mitigate bacterial virulence.