Early skin colonization by Staphylococcus epidermidis and Staphylococcus aureus reveals environment-dependent synergistic effects

Chrisse Ngari^1*Valerie Poulet²Giuseppe Percoco³Laurent Peno-Mazzarino³Damien Seyer⁴

• ¹Other, Paris, France
• ²Laboratoires Clarins SAS, Pontoise, France
• ³Eurofins BIO-EC, Longjumeau, France
• ⁴CY Cergy Paris Universite Equipe de Recherche sur les Relations Matrice Extracellulaire-Cellule, Cergy-Pontoise, France

Introduction: The skin microbiome is crucial for skin health and homeostasis. It contributes to immune defense, promotes epidermal differentiation, and supports a robust skin barrier function. Despite its importance, few studies have used model skin systems to examine how simple bacterial communities interact and how they impact the skin. Methods: We studied the interaction between a skin commensal, Staphylococcus epidermidis, and a pathogen, Staphylococcus aureus, by performing inoculations and co-inoculations on Reconstructed Human Epidermis (RHE) models maintained under classical humid conditions (>90% relative humidity) or dry conditions (<25% RH). In parallel, inoculations were conducted on human skin explants using a novel culture setup preserving physiological humidity levels (40-60% RH). Bacterial attachment was assessed four hours post-inoculation. At 24 hours, histology was examined, three natural moisturizing factors (NMFs) were quantified. Filaggrin (FLG) and ceramide levels were analyzed to assess the skin barrier function. Results: In contrast to previous findings at 24 hours, co-inoculation increased S. epidermidis and S. aureus attachment in RHEs, but only under humid conditions. Only RHE maintained in dry conditions and skin explant revealed an effect of co-inoculation on filaggrin (FLG), yet an increase in RHEs and a decrease in skin explants. In both RHEs maintained in dry conditions and skin explants, NMF levels were consistently reduced following co-inoculation. In RHEs and skin explants, inoculation with S. aureus alone also lowered NMFs, with co-inoculation further amplifying this effect. Finally, ceramide levels increased similarly across both inoculations and co-inoculation. Discussion: Revealing unexpected early interactions between S. epidermidis, S. aureus, and the skin, our results could suggest that co-inoculation may trigger a synergetic disruption of the barrier function. Alternatively, it could imply that co-inoculation might reinforce the epidermal barrier via a S. aureus-mediated stimulation of the protective functions of S. epidermidis. Further studies are needed to confirm these effects and determine whether they are strain-specific or more broadly applicable.