Understanding novel molecular interactions between bacteria and the skin in injury and infection

• Applicant: Dr. Nina Nathalie Schommer
• Subject Area: Dermatology
• Term: from 2011 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 202901829

The skin is the primary interface between the host and environmental microorganisms. An immune response to these pathogens and other environmental dangers are crucial to survival, but controlling the extent and duration of this response is equally important for health. Skin commensal bacteria play an important role in balancing the immune response thereby protecting the host from infection and uncontrolled inflammation. However, it is poorly understood how those bacteria interact with the cells of the skin in order to exert its effects. Recent observations of our group discovered that hyaluronan, a major glycosaminoglycan of tissue extracellular matrix and ligand for Toll-like receptor (TLR) 4 and TLR2 serves as a regulator of innate immune activation. Our data found that skin-specific bacteria of the genera Staphylococcus (S.) epidermidis as well as S. aureus bind hyaluronan. This novel observation might be the key explanation for how Staphylococci species initiate interaction with pattern recognition receptors. Digestion of hyaluronan in a mouse model that was engineered to overexpress hyaluronidase-1 in a tissue specific manner induced a decrease of the infectious outcome of Group A streptococcus (GAS). In contrast, the addition of high molecular weight hyaluronan to eukaryotic cells at the same time of infection with GAS significantly increased protection against phagocytosis thereby increasing the bacteriums virulence. Based on these observations we hypothesize that hyaluronan is important to the cutaneous defense strategy. Our overall aim includes defining the molecular mechanisms by which Staphylococci species interact with hyaluronan and the influence on this on virulence. Understanding the mechanisms by which hyaluronan modifies antimicrobial protection and inflammatory cell recruitment is essential to preventing inappropriate inflammation or abnormal susceptibility to infection and would provide excellent starting points for the development of new therapeutical strategies against skin diseases.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Richard Gallo