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<p>Metabolites derived from 33 lactic acid bacteria (LAB) isolates were screened for quorum sensing (QS) inhibitory activity against <i>Aeromonas hydrophila</i> using <i>Chromobacterium violaceum</i> as a biosensor. Three isolates (AZMS2, AZMFK2, and AZMDH7) showed the most consistent anti-QS activity, producing non-purple zones of 6.5, 6.3, and 4.8&#xa0;mm, respectively. Whole-genome sequencing identified AZMS2 and AZMDH7 as <i>Pediococcus acidilactici</i> and AZMFK2 as <i>Limosilactobacillus fermentum</i>, with biosynthetic gene clusters potentially associated with secondary metabolite production. Molecular docking revealed that a 5,12-naphthacenedione derivative from AZMFK2 showed the strongest binding affinity toward the QS receptor AhyR (− 7.69&#xa0;kcal/mol), followed by adenosine 3′,5′-cyclic monophosphate from AZMDH7 (-7.10&#xa0;kcal/mol) and 3,6-bis(benzyl)-tetrazine from AZMS2 (-6.78&#xa0;kcal/mol). Functionally, LAB metabolites exhibited &gt; 99.9% AHL degradation at 2&#xa0;mg/mL, inhibited biofilm formation by 77–79%, and reduced motility in <i>A. hydrophila</i>. In addition, RT-qPCR analysis revealed significant downregulation of QS-associated genes (<i>ahyI</i>, <i>ahyR</i>, and <i>aerA</i>), indicating interference with QS-regulated virulence at the transcriptional level. Collectively, these findings indicate that LAB-derived metabolites possess anti-QS and anti-virulence activity and may represent promising candidates for controlling <i>A. hydrophila</i>, particularly in aquaculture-associated settings.</p>

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Discovery of lactic acid bacteria metabolites as quorum sensing inhibitors suppressing Aeromonas hydrophila virulence

  • 期刊论文

  • 发表日期：

    2026年6月18日

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  • M. Fiqriansyah Wahab,
  • Nisa Rachmania Mubarik,
  • Baso Manguntungi,
  • Ariandi Ariandi,
  • Feraliana Feraliana,
  • Apon Zaenal Mustopa

摘要

Metabolites derived from 33 lactic acid bacteria (LAB) isolates were screened for quorum sensing (QS) inhibitory activity against Aeromonas hydrophila using Chromobacterium violaceum as a biosensor. Three isolates (AZMS2, AZMFK2, and AZMDH7) showed the most consistent anti-QS activity, producing non-purple zones of 6.5, 6.3, and 4.8 mm, respectively. Whole-genome sequencing identified AZMS2 and AZMDH7 as Pediococcus acidilactici and AZMFK2 as Limosilactobacillus fermentum, with biosynthetic gene clusters potentially associated with secondary metabolite production. Molecular docking revealed that a 5,12-naphthacenedione derivative from AZMFK2 showed the strongest binding affinity toward the QS receptor AhyR (− 7.69 kcal/mol), followed by adenosine 3′,5′-cyclic monophosphate from AZMDH7 (-7.10 kcal/mol) and 3,6-bis(benzyl)-tetrazine from AZMS2 (-6.78 kcal/mol). Functionally, LAB metabolites exhibited > 99.9% AHL degradation at 2 mg/mL, inhibited biofilm formation by 77–79%, and reduced motility in A. hydrophila. In addition, RT-qPCR analysis revealed significant downregulation of QS-associated genes (ahyI, ahyR, and aerA), indicating interference with QS-regulated virulence at the transcriptional level. Collectively, these findings indicate that LAB-derived metabolites possess anti-QS and anti-virulence activity and may represent promising candidates for controlling A. hydrophila, particularly in aquaculture-associated settings.