Studying the role of S. aureus and its biofilm in atopic dermatitis pathogenesis using in vitro 3D models

In recent years, AD skin microbiome has been widely studied, revealing a dysbiosis dominated by S. aureus (SA). Recently, the presence of SA biofilm in AD lesions has been described. Biofilm-associated bacteria show an innate resistance to antibiotics and host innate immune defense.
We used epidermal models to study the role of SA and its biofilm in AD and to evaluate a lipid-replenishing balm specifically formulated for infant with atopic skin.
Biofilm formation model: An inoculum of MRSA has been applied at the surface of reconstructed human epidermis (RHE). 6h and 24h after colonization, adhering bacteria were counted and biofilm formation at the epidermal surface was observed by scanning electron microscopy. The pre-treatment by the balm inhibited SA adhesion and decreased biofilm formation.
S.aureus-induced atopy model: RHE were infected with MRSA, then topically treated with the balm and set in co-culture with THP-1 cells. The model mimicked the main characteristics of atopic skin: barrier and immune response markers (Claudin1, hBD2, TLR2) were strongly inhibited while TSLP and Kallikrein-5 were overexpressed (qPCR analyses).
The balm decreased KLK5 and TSLP expression, suggesting an effect on KLK5-TSLP-PAR2 pathway linked to barrier dysfunction and itching in AD. It also induced TLR2, suggesting protective effect on immune defenses.
S. aureus-colonized epidermis models, in co-culture or not with immuno-competent cells, afford very complete models to understand molecular mechanisms involved in AD pathogenesis in response to S. aureus.

Ms Gaelle Bellemere