PLoS ONE (Jan 2014)

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

  • Anita Nielsen,
  • Maria Månsson,
  • Martin S Bojer,
  • Lone Gram,
  • Thomas O Larsen,
  • Richard P Novick,
  • Dorte Frees,
  • Hanne Frøkiær,
  • Hanne Ingmer

DOI
https://doi.org/10.1371/journal.pone.0084992
Journal volume & issue
Vol. 9, no. 1
p. e84992

Abstract

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Methicillin-resistant Staphylococcus aureus (MRSA) continues to be a serious human pathogen, and particularly the spread of community associated (CA)-MRSA strains such as USA300 is a concern, as these strains can cause severe infections in otherwise healthy adults. Recently, we reported that a cyclodepsipeptide termed Solonamide B isolated from the marine bacterium, Photobacterium halotolerans strongly reduces expression of RNAIII, the effector molecule of the agr quorum sensing system. Here we show that Solonamide B interferes with the binding of S. aureus autoinducing peptides (AIPs) to sensor histidine kinase, AgrC, of the agr two-component system. The hypervirulence of USA300 has been linked to increased expression of central virulence factors like α-hemolysin and the phenol soluble modulins (PSMs). Importantly, in strain USA300 Solonamide B dramatically reduced the activity of α-hemolysin and the transcription of psma encoding PSMs with an 80% reduction in toxicity of supernatants towards human neutrophils and rabbit erythrocytes. To our knowledge this is the first report of a compound produced naturally by a Gram-negative marine bacterium that interferes with agr and affects both RNAIII and AgrA controlled virulence gene expression in S. aureus.