Abstract
BackgroundSkin is the largest human neuroendocrine organ and hosts the second most numerous microbial population but the interaction of skin neuropeptides with the microflora has never been investigated. We studied the effect of Substance P (SP), a peptide released by nerve endings in the skin on bacterial virulence.Methodology/Principal Findings Bacillus cereus, a member of the skin transient microflora, was used as a model. Exposure to SP strongly stimulated the cytotoxicity of B. cereus (+553±3% with SP 10−6 M) and this effect was rapid (<5 min). Infection of keratinocytes with SP treated B. cereus led to a rise in caspase1 and morphological alterations of the actin cytoskeleton. Secretome analysis revealed that SP stimulated the release of collagenase and superoxide dismutase. Moreover, we also noted a shift in the surface polarity of the bacteria linked to a peel-off of the S-layer and the release of S-layer proteins. Meanwhile, the biofilm formation activity of B. cereus was increased. The Thermo unstable ribosomal Elongation factor (Ef-Tu) was identified as the SP binding site in B. cereus. Other Gram positive skin bacteria, namely Staphylococcus aureus and Staphylococcus epidermidis also reacted to SP by an increase of virulence. Thermal water from Uriage-les-Bains and an artificial polysaccharide (Teflose®) were capable to antagonize the effect of SP on bacterial virulence.Conclusions/SignificanceSP is released in sweat during stress and is known to be involved in the pathogenesis of numerous skin diseases through neurogenic inflammation. Our study suggests that a direct effect of SP on the skin microbiote should be another mechanism.
Highlights
Skin is the largest neuroendocrine organ of the human body [1] and it hosts the second most numerous microbial population [2]
We revealed that Substance P (SP) is acting on other Gram positive bacteria, namely Staphylococcus aureus and Staphylococcus epidermidis, suggesting that SP should act as a regulator of bacterial virulence in some of the principal skin associated bacteria
Cereus The study was realized on Bacillus cereus MFP01, a strain identified on the skin of normal human volunteers
Summary
Skin is the largest neuroendocrine organ of the human body [1] and it hosts the second most numerous microbial population [2]. Substance P (SP), the main neuropeptide identified in skin nerve endings, is essentially located in primary afferent C-fibers and is released in the skin [6] This undecapeptide of the tachykinin family has multiple bioactivities other than neurotransmission [7], such as capillary vasodilatation, fibroblast and keratinocyte proliferation or mast cell degranulation [1]. SP, contribute to the pathogenesis of numerous skin diseases, like psoriasis [10], atopic dermatitis [11,12], immediate and delayed hypersensitivity [13], acne [14] or rosacea [15] These diseases have multifactorial origins and we suggest that SP could act through interaction with the skin microflora. We studied the effect of Substance P (SP), a peptide released by nerve endings in the skin on bacterial virulence
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