title: Effects of a skin neuropeptide (substance p) on cutaneous microflora.
abstract: BACKGROUND
  Skin 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.
  
  
  RESULTS
  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
  SP 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.
authors.affiliation: Laboratory of Microbiology Signals and Microenvironnement LMSM, EA 4312, Normandie Université, Université Rouen, Evreux, France.
authors.forename: Lily
authors.initials: L
authors.lastname: Mijouin
authors.forename: Mélanie
authors.initials: M
authors.lastname: Hillion
authors.forename: Yasmina
authors.initials: Y
authors.lastname: Ramdani
authors.forename: Thomas
authors.initials: T
authors.lastname: Jaouen
authors.forename: Cécile
authors.initials: C
authors.lastname: Duclairoir-Poc
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Follet-Gueye
authors.forename: Elian
authors.initials: E
authors.lastname: Lati
authors.forename: Florent
authors.initials: F
authors.lastname: Yvergnaux
authors.forename: Azzedine
authors.initials: A
authors.lastname: Driouich
authors.forename: Luc
authors.initials: L
authors.lastname: Lefeuvre
authors.forename: Christine
authors.initials: C
authors.lastname: Farmer
authors.forename: Laurent
authors.initials: L
authors.lastname: Misery
authors.forename: Marc G J
authors.initials: MG
authors.lastname: Feuilloley
mesh_terms: D001409:Bacillus cereus / Q000254:growth & development / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development; D015740:Calcitonin Gene-Related Peptide; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D009490:Neurosecretory Systems / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000378:metabolism* / Q000472:pathogenicity; D013373:Substance P / Q000378:metabolism*; D014774:Virulence / Q000235:genetics
chemical_list: D013373:Substance P; D015740:Calcitonin Gene-Related Peptide