Substance P and Calcitonin Gene-Related Peptide: Key Regulators of Cutaneous Microbiota Homeostasis

Awa N’diaye (1) , Andrei Gannesen (1) , Valérie Borrel (1) , Olivier Maillot (1) , Jeremy Enaut (1) , Pierre-Jean Racine (1) , Vladimir Plakunov (2) , Sylvie Chevalier (1) , Olivier Lesouhaitier (1) , Marc Feuilloley (1)

1 LMSM - Laboratoire de Microbiologie Signaux et Microenvironnement
2 Winogradsky Institute of Microbiology [Moscow]

Neurohormones diffuse in sweat and epidermis leading skin bacterial microflora to be largely exposed to these host factors. Bacteria can sense a multitude of neurohormones, but their role in skin homeostasis was only investigated recently. The first study focused on substance P (SP), a neuropeptide produced in abundance by skin nerve terminals. SP is without effect on the growth of Gram-positive (Bacillus cereus, Staphylococcus aureus, and Staphylococcus epidermidis) and Gram-negative (Pseudomonas fluorescens) bacteria. However, SP is stimulating the virulence of Bacillus and Staphylococci. The action of SP is highly specific with a threshold below the nanomolar level. Mechanisms involved in the response to SP are different between bacteria although they are all leading to increased adhesion and/or virulence. The moonlighting protein EfTu was identified as the SP-binding site in B. cereus and Staphylococci. In skin nerve terminals, SP is co-secreted with the calcitonin gene-related peptide (CGRP), which was shown to modulate the virulence of S. epidermidis. This effect is antagonized by SP. Identification of the CGRP sensor, DnaK, allowed understanding this phenomenon as EfTu and DnaK are apparently exported from the bacterium through a common system before acting as SP and CGRP sensors. Many other neuropeptides are expressed in skin, and their potential effects on skin bacteria remain to be investigated. Integration of these host signals by the cutaneous microbiota now appears as a key parameter in skin homeostasis.

Mots clés: skin bacterial communication; substance P; calcitonin gene-related peptide; DnaK chaperone protein; efTu thermo unstable ribosomal elongation factor; MscL mechanosensitive channel; moonlighting proteins; microbial endocrinology

Domaines: Microbiologie et Parasitologie

Awa N’diaye, Andrei Gannesen, Valérie Borrel, Olivier Maillot, Jeremy Enaut, et al.. Substance P and Calcitonin Gene-Related Peptide: Key Regulators of Cutaneous Microbiota Homeostasis. Frontiers in Endocrinology, 2017, 8, ⟨10.3389/fendo.2017.00015⟩. ⟨hal-01886556⟩