Defense Mechanisms during Microbial Hair Follicle Invasion

The bacterium Staphylococcus aureus (SA) can cause lethal infections and is notorious for its antibiotic resistance, which stresses the development of alternative treatment strategies. It also represents an excellent example of a commensal bacterium with the potential to become an opportunistic pathogen. Hair follicles are an important niche for commensal skin bacteria, but also depict a weakness in the epidermal barrier that can be exploited by the microbes. Especially, novel hair shaft eruption is an immunologically relevant event that can trigger skin barrier disruption and microbial invasion. If not properly orchestrated, it facilitates SA dominated dysbiosis and wide-spread skin disease. The epidermal growth factor receptor (EGFR) is crucially involved in this process. As many solid tumors over-express EGFR, EGFR- inhibitors are successfully used as targeted anti-cancer treatment. The importance of EGFR to the skin is reflected by the therapys adverse events. These consist of acneiform eruptions in the face and trunk. During long-term treatment, SA superinfections exacerbate the inflammation, which severely hampers cancer therapy success. This project aims to identify the molecular mechanism underlying the antibacterial importance of EGFR in the hair follicle during bacterial hair follicle invasion, the cellular localization of this anti-bacterial machinery and its therapeutic potential. Understanding these processes will allow to specifically target bacterial skin and hair infections and additionally manage adverse events during targeted anti- cancer therapy to improve its efficacy.