Journal article
Solonamide B Inhibits Quorum Sensing and Reduces Staphylococcus aureus Mediated Killing of Human Neutrophils
University of Copenhagen1
Department of Systems Biology, Technical University of Denmark2
Natural Product Chemistry, Department of Systems Biology, Technical University of Denmark3
Bacterial Ecophysiology and Biotechnology, Department of Systems Biology, Technical University of Denmark4
New York University School of Medicine5
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 a-hemolysin and the phenol soluble modulins (PSMs).
Importantly, in strain USA300 Solonamide B dramatically reduced the activity of a-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.
Language: | English |
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Publisher: | Public Library of Science |
Year: | 2014 |
Pages: | e84992 |
ISSN: | 15537358 , 1553734x and 19326203 |
Types: | Journal article |
DOI: | 10.1371/journal.pone.0084992 |
ORCIDs: | 0000-0002-8488-9593 , 0000-0002-8350-5631 , Gram, Lone and Larsen, Thomas Ostenfeld |
Agr protein, Staphylococcus aureus AgrC protein, Staphylococcus Animals Bacterial Proteins Bacterial Toxins Erythrocytes Gene Expression Regulation, Bacterial Hemolysin Proteins Humans Medicine Methicillin-Resistant Staphylococcus aureus Neutrophils Peptides, Cyclic Photobacterium Primary Cell Culture Protein Kinases Q Quorum Sensing R Rabbits Science Trans-Activators Virulence solomonamide B staphylococcal alpha-toxin staphylococcal delta toxin