Solonamide B Inhibits Quorum Sensing and Reduces Staphylococcus Aureus Mediated Killing of Human Neutrophils

PLoS One. 2014 Jan 8;9(1):e84992. doi: 10.1371/journal.pone.0084992. eCollection 2014.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / antagonists & inhibitors
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Bacterial Toxins / antagonists & inhibitors
  • Bacterial Toxins / genetics
  • Bacterial Toxins / metabolism
  • Erythrocytes / drug effects
  • Erythrocytes / microbiology
  • Gene Expression Regulation, Bacterial*
  • Hemolysin Proteins / antagonists & inhibitors
  • Hemolysin Proteins / genetics
  • Hemolysin Proteins / metabolism
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / genetics
  • Methicillin-Resistant Staphylococcus aureus / pathogenicity
  • Neutrophils / drug effects
  • Neutrophils / microbiology*
  • Peptides, Cyclic / isolation & purification
  • Peptides, Cyclic / pharmacology*
  • Photobacterium / chemistry
  • Primary Cell Culture
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Quorum Sensing / drug effects*
  • Quorum Sensing / genetics
  • Rabbits
  • Trans-Activators / antagonists & inhibitors
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Virulence

Substances

  • Agr protein, Staphylococcus aureus
  • Bacterial Proteins
  • Bacterial Toxins
  • Hemolysin Proteins
  • Peptides, Cyclic
  • Trans-Activators
  • solomonamide B
  • staphylococcal alpha-toxin
  • staphylococcal delta toxin
  • Protein Kinases
  • AgrC protein, Staphylococcus

Grant support

This work was supported by funding from the Programme Committee for Food, Health and Welfare under the Danish Strategic Research Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.