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Identity and effects of quorum-sensing inhibitors produced by Penicillium species

Thomas Bovbjerg Rasmussen1, Mette E Skindersoe1, Thomas Bjarnsholt1

  • 1Center for Biomedical Microbiology, BioCentrum-DTU, Technical University of Denmark, DK-2800 Kgs. Lyngby, Denmark.

Microbiology (Reading, England)
|May 5, 2005
PubMed

Insights

Fungal compounds patulin and penicillic acid inhibit bacterial quorum sensing (QS) in Pseudomonas aeruginosa. This QS inhibition enhances antibiotic susceptibility and boosts immune response, leading to faster infection clearance in mice.

Area of Science:

  • Microbiology
  • Medical Mycology
  • Pharmacology

Background:

  • Quorum sensing (QS) is a bacterial communication system enabling virulence, exemplified by Pseudomonas aeruginosa infections in immunocompromised individuals.
  • Blocking QS in P. aeruginosa attenuates virulence and increases biofilm susceptibility to antibiotics.
  • Fungi produce secondary metabolites with antimicrobial properties and may possess compounds that interfere with bacterial QS.

Purpose of the Study:

  • To screen fungal extracts for compounds that inhibit bacterial QS.
  • To identify specific fungal metabolites with QS inhibitory (QSI) activity.
  • To evaluate the therapeutic potential of identified QSI compounds against P. aeruginosa infections.

Main Methods:

  • Screening of 100 extracts from 50 Penicillium species for QS inhibitory activity.
  • Identification of active compounds using chemical analysis.
  • Verification of QSI effects on P. aeruginosa gene expression via DNA microarray transcriptomics.
  • Assessment of biofilm susceptibility to antibiotics and immune cell activation.
  • Evaluation in a mouse pulmonary infection model.

Main Results:

  • 33 of 100 fungal extracts exhibited QS inhibitory activity.
  • Patulin and penicillic acid were identified as active QSI compounds.
  • Patulin enhanced biofilm susceptibility to tobramycin and activated neutrophils.
  • Patulin treatment led to more rapid clearance of P. aeruginosa in a mouse model.

Conclusions:

  • Fungal metabolites, specifically patulin and penicillic acid, are effective QS inhibitors.
  • These QSI compounds demonstrate potential for novel therapeutic strategies against P. aeruginosa.
  • Inhibition of QS by fungal compounds can restore antibiotic efficacy and enhance host immune response.

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