Abstract
Staphylococcus aureus and Staphylococcus epidermidis 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 S. aureus and S. epidermidis 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 Staphylococci 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 S. aureus and S. epidermidis, we observed that SP increases the adhesion potential of both bacteria on keratinocytes. However, SP modulates the virulence of S. aureus and S. epidermidis through different mechanisms. The response of S. aureus is associated with an increase in Staphylococcal Enterotoxin C2 (SEC2) production and a reduction of exolipase processing whereas in S. epidermidis 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 S. aureus and S. epidermidis. SP appears as an inter-kingdom communication factor involved in the regulation of bacterial virulence and essential for skin microflora homeostasis.
Highlights
Skin is a complex ecosystem including yeasts, fungi, bacteria, and viruses (Kong and Segre, 2012) and it is estimated that one billion bacteria colonize each square centimeter of skin (Grice et al, 2008)
As Ef-Tu was previously identified as the Substance P (SP)-binding site in B. cereus (Mijouin et al, 2013), we studied the identity of the SP binding protein in S. aureus and S. epidermidis by WesternBlot using polyclonal anti-Ef-Tu antibodies
The effect of SP on S. epidermidis was similar with a reduction of reconstructed human epidermidis (RHE) viability of 11.63 ± 0.01 and 19.70 ± 0.01% after incubation with bacterial culture (107 or 108 CFU/mL, p < 0.001, respectively; Figure 1B)
Summary
Skin is a complex ecosystem including yeasts, fungi, bacteria, and viruses (Kong and Segre, 2012) and it is estimated that one billion bacteria colonize each square centimeter of skin (Grice et al, 2008). Almost 25% of the microbial population is located deeply into the skin through hair follicles, sweat, and sebaceous glands (Lange-Asschenfeldt et al, 2011) and is in close contact with eukaryotic cells It has been known since the end of the twentieth century that bacteria can sense a large range of eukaryotic communication and defense molecules (Lesouhaitier et al, 2009). The principal skin neuropeptide, Substance P (SP), released by sensory skin primary afferent C-fibers (Severini et al, 2002) shows important variations of local concentration under the effect of pain, stress, and infection (Harrison and Geppetti, 2001; Nakano, 2004; O’Connor et al, 2004). The basal concentration of antimicrobial peptides in skin is low and under the minimal inhibitory bacterial concentration (Lai and Gallo, 2009), it has been observed that antimicrobial peptides are detected by bacteria at sub-lethal doses (Hancock and Scott, 2000) where they can induce an unexpected increase of virulence (Madi et al, 2013)
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