The role of antimicrobial peptides in human skin infections
Project team: Sabine Gabrysch
External collaborators: Philipp Zanger
Funding: Core funding
Funding period: 2009-2010
Staphylococcus aureus is the most common cause of skin infections. Presentation and course of disease vary from minor self-limiting infections to deep, recurrent abscesses that require surgical intervention and systemic antibiotic therapy. A possible explanation for these differences in disease susceptibility and severity has been provided by recent insights into innate defence mechanisms of human skin, in particular antimicrobial peptides (AMP). These are natural antibiotics present in the skin that are thought to prevent infection in the first place, or that can be upregulated in response to infection and limit the severity of disease.
In the travel clinic of the Institute of Tropical Medicine in Tüingen, studies were conducted among travellers returning with Staphylococcus aureus-positive skin infection (cases) and healthy control subjects.
When examining healthy skin (from the gluteal region) from both cases and controls, we could show that expression of the antimicrobial peptide RNase 7 was 64% higher in the skin of control subjects than in the skin of cases, while there was no difference in the expression of the antimicrobial peptides HBD-2 and HBD-3. Together with the known high baseline expression of RNase 7, this suggests that this AMP confers protection against skin infection.
In those travellers with skin infection, we furthermore examined AMP inducibility (upregulation) by comparing AMP levels in infected skin to that in healthy skin. Both HBD-2 and HBD-3 were strongly upregulated by S. aureus infection, but not RNase 7. When comparing inducibility between patients with different severity of skin infection, we found that expression of HBD-3 was 11 times lower in patients with more than 6 recurrences and 9 times lower in patients reporting surgical drainage than in the respective baseline groups. There was no difference in HBD-2 inducibility between severity groups. This suggests that high inducibility of HBD-3 can limit the severity of skin infection.
Zanger P, Nurjadi D, Gaile M, Gabrysch S, Kremsner PG. (2012): Hormonal contraceptive use and persistent Staphylococcus aureus nasal carriage. Clinical Infectious Diseases, 55(12):1625-1632.
Zanger P, Holzer J, Schleucher R, Steffen H, Schittek B, Gabrysch S. (2009): Constitutive Expression of the Antimicrobial Peptide RNase 7 is Associated with Staphylococcus aureus Infection of the Skin. Journal of Infectious Diseases, 200(12):1907-15.
Zanger P, Holzer J, Schleucher R, Scherbaum MD, Schittek B, Gabrysch S. (2010): Severity of Staphylococcus aureus Infection of the Skin is Associated with Inducibility of Human β-Defensin 3, but not Human β-Defensin 2. Infection and Immunity, 78(7):3112-7.