Phevalin (aureusimine B) production by Staphylococcus aureus biofilm and impacts on human keratinocyte gene expression.
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.
Center for Biofilm Engineering, Montana State University, Bozeman, Montana, United States of America. psecor@uw.edu
Patrick R
PR
Secor
Laura K
LK
Jennings
Garth A
GA
James
Kelly R
KR
Kirker
Elinor Delancey
ED
Pulcini
Kate
K
McInnerney
Robin
R
Gerlach
Tom
T
Livinghouse
Jonathan K
JK
Hilmer
Brian
B
Bothner
Philip
P
Fleckman
John E
JE
Olerud
Philip S
PS
Stewart
D017209:Apoptosis / Q000187:drug effects; D018441:Biofilms / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D055442:Metabolome / Q000187:drug effects; D020543:Proteome / Q000378:metabolism; D011719:Pyrazines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000502:physiology*
D017077:Culture Media, Conditioned; D020543:Proteome; D011719:Pyrazines; C096976:phevalin