Regulation of cell cycle and differentiation markers by pathogenic, non-pathogenic and opportunistic skin bacteria

Abstract Skin is the first line of defense against the physical, chemical and the biological environment. It is an ideal organ for studying molecular responses to biological infections through a variety of skin cells that specialize in immune responses. Comparative analysis of skin response to pathogenic, non-pathogenic, and commensal bacteria would help in the identification of disease specific pathways for drug targets. In this study, we investigated human breast reduction skin responses to Cutibacterium acnes (C. acnes), Staphylococcus aureus (S. aureus), Staphylococcus epidermidis (S. epidermidis), and TLR1/2 agonist using Affymetrix microarray chips. The Pam3CSK4 solution and bacterial cultures were prepared and inoculated in steel rings, that were placed on the acetone treated epidermis in a petri dish. After 24h incubation, 8mm punch biopsies were taken from the center of the ring, and RNA was extracted. The genome-wide expression was then analyzed using Affymetrix HG-133A gene chip microarray. We found that the C. acnes and S. aureus boosted the production of extracellular matrix components and attenuated the expression of differentiation markers. The above responses were mediated through the TLR2 pathway. Skin also responded to S. aureus and C. acnes by inducing the genes of the cell cycle machinery; this response was not TLR2-dependent. S. aureus induced, whereas C. acnes suppressed the genes associated with apoptosis; this was also not TLR2-dependent. Moreover, S. epidermis apparently did not lead to changes in gene expression. We conclude that the breast reduction skin is a very useful model to study the global gene expression in response to bacterial treatments.