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.
Highlights
Staphylococcus aureus is a serious human pathogen that causes a variety of diseases, such as skin and soft tissue infections, bacteremia, and toxic shock syndrome [1,2]
In a search for compounds that reduce virulence gene expression in S. aureus we discovered that Solonamide B which is produced by a marine Photobacterium halotolerans, reduces expression of a-hemolysin and rnaIII and increases expression of spa encoding protein A in both strain 83254 and USA300 [34]
Solonamide B Interferes with agr Activation From the marine bacterium Photobacterium halotolerans we recently identified a cyclodepsipeptide, Solonamide B that interferes with virulence gene expression in S. aureus without inhibiting growth
Summary
Staphylococcus aureus is a serious human pathogen that causes a variety of diseases, such as skin and soft tissue infections, bacteremia, and toxic shock syndrome [1,2]. While the hospital associated S. aureus strains are generally opportunistic pathogens incapable of infecting healthy individuals [5] a more aggressive group of strains have emerged since the early 1990s that is both highly virulent and transmissible giving rise to infections in the community, termed community associated, methicillin resistant strains (CA-MRSA). The CA-MRSA strains belong to several sequence types with USA300 (ST8) being the most common in the US [6,7]. These strains are able to infect healthy individuals often giving rise to skin and soft tissue infections that in some instances may turn out to be lethal [8,9]
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