title: Skin-bacteria communication: Involvement of the neurohormone Calcitonin Gene Related Peptide (CGRP) in the regulation of Staphylococcus epidermidis virulence.
abstract: Staphylococci can sense Substance P (SP) in skin, but this molecule is generally released by nerve terminals along with another neuropeptide, Calcitonin Gene Related Peptide (CGRP). In this study, we investigated the effects of αCGRP on Staphylococci. CGRP induced a strong stimulation of Staphylococcus epidermidis virulence with a low threshold (<10-12M) whereas Staphylococcus aureus was insensitive to CGRP. We observed that CGRP-treated S. epidermidis induced interleukin 8 release by keratinocytes. This effect was associated with an increase in cathelicidin LL37 secretion. S. epidermidis displayed no change in virulence factors secretion but showed marked differences in surface properties. After exposure to CGRP, the adherence of S. epidermidis to keratinocytes increased, whereas its internalization and biofilm formation activity were reduced. These effects were correlated with an increase in surface hydrophobicity. The DnaK chaperone was identified as the S. epidermidis CGRP-binding protein. We further showed that the effects of CGRP were blocked by gadolinium chloride (GdCl3), an inhibitor of MscL mechanosensitive channels. In addition, GdCl3inhibited the membrane translocation of EfTu, the Substance P sensor. This work reveals that through interaction with specific sensors S. epidermidis integrates different skin signals and consequently adapts its virulence.
authors.affiliation: Laboratory of Microbiology Signals and Microenvironnement, LMSM, EA 4312, Normandie Université, Evreux, France.
authors.forename: Awa R
authors.initials: AR
authors.lastname: N'Diaye
authors.affiliation: Laboratory of Microbiology Signals and Microenvironnement, LMSM, EA 4312, Normandie Université, Evreux, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Leclerc
authors.affiliation: Laboratory of Polymers, Biopolymers and Surfaces, CNRS UMR 6270, Normandie Université, Mont-Saint-Aignan, France.
authors.forename: Takfarinas
authors.initials: T
authors.lastname: Kentache
authors.affiliation: Laboratory of Polymers, Biopolymers and Surfaces, CNRS UMR 6270, Normandie Université, Mont-Saint-Aignan, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Hardouin
authors.affiliation: Laboratory of Microbiology Signals and Microenvironnement, LMSM, EA 4312, Normandie Université, Evreux, France.
authors.forename: Cecile Duclairoir
authors.initials: CD
authors.lastname: Poc
authors.affiliation: Laboratory of Microbiology Signals and Microenvironnement, LMSM, EA 4312, Normandie Université, Evreux, France.
authors.forename: Yoan
authors.initials: Y
authors.lastname: Konto-Ghiorghi
authors.affiliation: Laboratory of Microbiology Signals and Microenvironnement, LMSM, EA 4312, Normandie Université, Evreux, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevalier
authors.affiliation: Laboratory of Microbiology Signals and Microenvironnement, LMSM, EA 4312, Normandie Université, Evreux, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Lesouhaitier
authors.affiliation: Laboratory of Microbiology Signals and Microenvironnement, LMSM, EA 4312, Normandie Université, Evreux, France.
authors.forename: Marc G J
authors.initials: MG
authors.lastname: Feuilloley
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D018441:Biofilms / Q000254:growth & development; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics* / Q000378:metabolism; D005682:Gadolinium / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000382:microbiology; D009411:Nerve Endings / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D009479:Neuropeptides / Q000187:drug effects / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D013203:Staphylococcal Infections / Q000235:genetics / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000378:metabolism / Q000472:pathogenicity; D013212:Staphylococcus epidermidis / Q000378:metabolism* / Q000472:pathogenicity; D013373:Substance P / Q000378:metabolism; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D016209:Interleukin-8; D009479:Neuropeptides; D013373:Substance P; D005682:Gadolinium; D015740:Calcitonin Gene-Related Peptide; C038958:gadolinium chloride; D054804:Cathelicidins