AUTHOR=N'Diaye Awa , Mijouin Lily , Hillion Mélanie , Diaz Suraya , Konto-Ghiorghi Yoan , Percoco Giuseppe , Chevalier Sylvie , Lefeuvre Luc , Harmer Nicholas J. , Lesouhaitier Olivier , Feuilloley Marc G. J. 

TITLE=Effect of Substance P in Staphylococcus aureus and Staphylococcus epidermidis Virulence: Implication for Skin Homeostasis

JOURNAL=Frontiers in Microbiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2016.00506

DOI=10.3389/fmicb.2016.00506

ISSN=1664-302X

ABSTRACT=<p><italic>Staphylococcus aureus</italic> and <italic>Staphylococcus epidermidis</italic> are two major skin associated bacteria, and Substance P (SP) is a major skin neuropeptide. Since bacteria are known to sense and response to many human hormones, we investigated the effects of SP on Staphylococci virulence in reconstructed human epidermis model and HaCaT keratinocytes. We show that SP is stimulating the virulence of <italic>S. aureus</italic> and <italic>S. epidermidis</italic> in a reconstructed human epidermis model. qRT-PCR array analysis of 64 genes expressed by keratinocytes in the response to bacterial infection revealed a potential link between the action of SP on <italic>Staphylococci</italic> and skin physiopathology. qRT-PCR and direct assay of cathelicidin and human β-defensin 2 secretion also provided that demonstration that the action of SP on bacteria is independent of antimicrobial peptide expression by keratinocytes. Considering an effect of SP on <italic>S. aureus</italic> and <italic>S. epidermidis</italic>, we observed that SP increases the adhesion potential of both bacteria on keratinocytes. However, SP modulates the virulence of <italic>S. aureus</italic> and <italic>S. epidermidis</italic> through different mechanisms. The response of <italic>S. aureus</italic> is associated with an increase in Staphylococcal Enterotoxin C2 (SEC2) production and a reduction of exolipase processing whereas in <italic>S. epidermidis</italic> the effect of SP appears mediated by a rise in biofilm formation activity. The Thermo unstable ribosomal Elongation factor Ef-Tu was identified as the SP-interacting protein in <italic>S. aureus</italic> and <italic>S. epidermidis</italic>. SP appears as an inter-kingdom communication factor involved in the regulation of bacterial virulence and essential for skin microflora homeostasis.</p>