Solonamide B inhibits quorum sensing and reduces Staphylococcus aureus mediated killing of human neutrophils

Anita Nielsen1, Maria Månsson2, Martin S Bojer1

  • 1Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Plos One
|January 14, 2014
PubMed

Insights

Marine bacterium Solonamide B disrupts Staphylococcus aureus (MRSA) virulence. This compound inhibits the agr quorum sensing system, reducing toxins and decreasing USA300 strain infection severity.

Area of Science:

  • Microbiology
  • Marine Biology
  • Pathogen Research

Background:

  • Methicillin-resistant Staphylococcus aureus (MRSA), particularly community-associated (CA)-MRSA USA300, causes severe infections.
  • The agr quorum sensing system regulates MRSA virulence factors.
  • Solonamide B, a cyclodepsipeptide from Photobacterium halotolerans, was previously shown to reduce RNAIII expression.

Purpose of the Study:

  • To investigate Solonamide B's mechanism of action on the agr system.
  • To evaluate Solonamide B's effect on MRSA USA300 virulence factors and toxicity.

Main Methods:

  • Investigated Solonamide B's interference with autoinducing peptide (AIP) binding to AgrC.
  • Assessed Solonamide B's impact on alpha-hemolysin activity and PSM transcription in USA300.
  • Measured the toxicity of USA300 supernatants on human neutrophils and rabbit erythrocytes.

Main Results:

  • Solonamide B inhibits the binding of AIPs to AgrC, disrupting the agr quorum sensing system.
  • Solonamide B significantly reduced alpha-hemolysin activity and PSM transcription in MRSA USA300.
  • Supernatant toxicity was reduced by 80% towards human neutrophils and rabbit erythrocytes.

Conclusions:

  • Solonamide B is the first reported natural compound from a marine Gram-negative bacterium to interfere with MRSA agr quorum sensing.
  • Solonamide B effectively reduces MRSA USA300 virulence gene expression and associated toxicity.

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