Journal Article

Phevalin (aureusimine B)Production by Staphylococcus aureus Biofilm and Impacts on Human Keratinocyte Gene Expression

Olerud, John E., Bothner, Brian, Jennings, Laura K., McInnerney, Kate, Kirker, Kelly R., Stewart, Philip S., Livinghouse, Tom, Fleckman, Philip, Hilmer, Jonathan K., James, Garth A., Pulcini, Elinor deLancey, Gerlach, Robin, Secor, Patrick R.

2012

Overview

Staphylococcus aureus biofilms are associated with chronic skin infections and are orders of magnitude more resistant to antimicrobials and host responses. S. aureus contains conserved nonribosomal peptide synthetases that produce the cyclic dipeptides tyrvalin and phevalin (aureusimine A and B, respectively). The biological function of these compounds has been speculated to be involved in virulence factor gene expression in S. aureus, protease inhibition in eukaryotic cells, and interspecies bacterial communication. However, the exact biological role of these compounds is unknown. Here, we report that S. aureus biofilms produce greater amounts of phevalin than their planktonic counterparts. Phevalin had no obvious impact on the extracellular metabolome of S. aureus as measured by high-performance liquid chromatography-mass spectrometry and nuclear magnetic resonance. When administered to human keratinocytes, phevalin had a modest effect on gene expression. However, conditioned medium from S. aureus spiked with phevalin amplified differences in keratinocyte gene expression compared to conditioned medium alone. Phevalin may be exploited as potential biomarker and/or therapeutic target for chronic, S. aureus biofilm-based infections.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Antimicrobial agents / Apoptosis / Apoptosis - drug effects / Bacteria / Biochemistry / Biofilms / Biofilms - drug effects / Bioindicators / Bioinformatics / Biology / Biomarkers / Biosynthesis / Broadway theater / Cell cycle / Chemistry / Chromatography / Chromatography, High Pressure Liquid / Conditioning / Culture Media, Conditioned - pharmacology / Cyclic dipeptides / Dermatology / Drosophila melanogaster / Engineering / Extracellular Space - drug effects / Extracellular Space - metabolism / Gene expression / Gene Expression Regulation - drug effects / Genes / Genomics / Growth factors / Health aspects / High performance liquid chromatography / Humans / Infections / Insects / Keratinocytes / Keratinocytes - drug effects / Keratinocytes - metabolism / Kinases / Liquid chromatography / Magnetic resonance / Magnetic Resonance Spectroscopy / Mass Spectrometry / Mass spectroscopy / Medicine / Metabolites / Metabolome - drug effects / NMR / Nuclear magnetic resonance / Pathogens / Peptides / Phosphorylation / Proteases / Proteome - metabolism / Pyrazines - chemistry / Pyrazines - metabolism / Pyrazines - pharmacology / Scientific imaging / Secor, Laura / Skin / Staphylococcal infections / Staphylococcus aureus / Staphylococcus aureus - drug effects / Staphylococcus aureus - physiology / Surfactants / Therapeutic applications / Virulence / Virulence factors