Inhibition of Microbial Quorum Sensing Mediated Virulence Factors by Pestalotiopsis sydowiana

Paramanantham Parasuraman1, B Devadatha2, V Venkateswara Sarma2

  • 1Department of Microbiology, School of Life Sciences, Pondicherry University, Puducherry 605014, India.

Insights

Marine fungus extract effectively inhibits Pseudomonas aeruginosa virulence by disrupting quorum sensing (QS). This study identifies potent compounds that reduce bacterial infection factors, offering a novel strategy against antibiotic-resistant pathogens.

Area of Science:

  • Marine microbiology and natural product chemistry
  • Antimicrobial drug discovery and development
  • Bacterial pathogenesis and virulence factor inhibition

Background:

  • Quorum sensing (QS) mediated infections pose significant health risks, necessitating alternative strategies to combat antibiotic-resistant bacteria.
  • Marine fungi represent a rich source of bioactive compounds with potential antipathogenic properties.
  • Pseudomonas aeruginosa infections are a major concern due to their virulence and resistance to conventional antibiotics.

Purpose of the Study:

  • To evaluate the antipathogenic potential of the marine fungus Pestalotiopsis sydowiana PPR extract against Pseudomonas aeruginosa.
  • To investigate the effect of fungal extract and its metabolites on QS-regulated virulence factors and biofilm formation.
  • To identify and characterize the specific bioactive compounds responsible for the observed antivirulence activity.

Main Methods:

  • Determination of the minimum inhibitory concentration (MIC) of fungal extract and identified compounds against P. aeruginosa PAO1.
  • Assessment of sub-MIC effects on QS-controlled virulence factors (pyocyanin, protease, elastase, etc.) and exopolysaccharide production.
  • In silico analysis of metabolite-receptor interactions and identification of potent compounds (Cyclo(-Leu-Pro) and 4-Hydroxyphenylacetamide) using computational approaches.

Main Results:

  • Sub-MIC concentrations of P. sydowiana PPR extract significantly reduced pyocyanin, chitinase, protease, elastase, and staphylolytic activity.
  • The extract also inhibited exopolysaccharide, rhamnolipid, and alginate production, leading to a substantial reduction in biofilm formation (90.54%).
  • In silico analysis identified Cyclo(-Leu-Pro) and 4-Hydroxyphenylacetamide as key metabolites binding to QS receptors (LasR and RhlR), with significant antivirulence effects observed at sub-MIC levels.

Conclusions:

  • Metabolites from Pestalotiopsis sydowiana PPR exhibit potent quorum sensing inhibitory activity against Pseudomonas aeruginosa.
  • These findings highlight the potential of marine fungal-derived compounds as novel antipathogenic agents to combat bacterial infections.
  • The identified compounds, Cyclo(-Leu-Pro) and 4-Hydroxyphenylacetamide, represent promising candidates for developing new anti-virulence therapies.

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