E-GEOD-32920 - Phevalin (aureusimine B) production by Staphylococcus aureus biofilm and impacts on human keratinocyte gene expression
Released on 1 October 2012, last updated on 18 October 2012
Staphylococcus aureus produces the cyclic dipeptides tyrvalin and phevalin (aureusimine A and B, respectively). A previous study reported that S. aureus mutants not capable of producing these compounds were less virulent in vivo through the deranged regulation of virulence factor genes. These findings, however, have been questioned as an unknown mutation in an operon that regulates virulence was discovered in the mutant strain. Here, we report that S. aureus biofilms produce greater amounts of phevalin than their planktonic counterparts. When administered to human keratinocytes, phevalin had no substantial effect on gene expression. Phevalin had no obvious impact on the extracellular metabolome of S. aureus. However, conditioned medium from S. aureus spiked with phevalin resulted in significant differences in keratinocyte gene expression compared to conditioned medium alone. A role for phevalin in manipulating host responses is apparent. Additionally, phevalin is a potential biomarker and/or therapeutic target for chronic, biofilm-based infections. Secreted factors from S. aureus biofilm and planktonic cultures with equivalent population sizes were placed in contact with human HaCaT keratinocytes for 4 hours. Keratinocytes were grown to ~90% confluency.
transcription profiling by array
Brian Bothner, Garth A James, John E Olerud, Jonathan K Hilmer, Kate McInnerney, Kelly R Kirker, Laura K Jennings, Patrick R Secor, Philip Fleckman, Philip S Stewart, Robin Gerlach, Tom Livinghouse