Impact and Determinants of Staphylococcus aureus Colonization and Infection

Staphylococcus aureus as commensal and pathogen has gained enormous attention over the last few years, because of increasing virulence, antimicrobial resistance, and the epidemic occurrence of associated infections. The human skin and mucosae are the primary reservoir of S. aureus. Persistently colonized individuals have been shown to be at a high risk of acquiring a range of S. aureus related diseases – from skin and soft tissue infection to sepsis. Besides, it is known that persistent carriage plays a role in the dispersion of S. aureus in the environment and promotes the development of resistance against antibiotics through horizontal genetic exchange followed by selection of resistant clones under antibiotic pressure. Taken together, colonization is a key factor for the evolution of infection and antimicrobial resistance.

The host-factors promoting S. aureus colonization are largely enigmatic. Antimicrobial peptides (AMP) as part of the primary skin defense are thought to play a key role in shaping the human skin microbiome. Human β-Defensin-3 (hBD-3) and RNase7 are highly active against S. aureus in vitro and are constitutively expressed in healthy, non-inflamed skin, but can be induced through various stimuli. Interestingly, there is inter-individual variation in AMP-expression suggesting that mechanisms involved in AMP regulation are important determinants of S. aureus colonization.

Our group focuses on the role of innate immune mechanisms as determinant for colonization and infection with S. aureus. Previously, we have shown that lower expression of hBD-3 and RNase7 increases susceptibility of human skin to S. aureus colonization and infection. Current projects study the interplay of cell-mediated immunity and AMP expression in human skin and try to identify those pathways that account for the inter-individual variation in AMP-expression in human skin and keratinocytes. We use a combination of in vitro models, human in vivo and ex vivo experiments as well as genetic association studies to provide comprehensive evidence on both, the functional and population relevance of involved host-factors.

Closely linked to this work are studies on the emergence and global spread of antimicrobial resistant S. aureus through colonized and infected travellers. These research projects are conducted in collaboration with a network of researchers at travel clinics across Europe and microbiologists around the globe. For further information on the European Network on Imported S. aureus, please visit the network’s homepage at www.staphtrav.eu.

Selected publications

1. Nurjadi D, Herrmann E, Hinderberger I, Zanger P (2013) Impaired β-defensin expression in human skin links DEFB1 promoter polymorphisms with persistent Staphylococcus aureus nasal carriage Journal of Infectious Diseases 207:666-74
2. Zanger P, Nurjadi D, Schleucher R, Scherbaum H, Wolz C, Kremsner PG, Schulte B (2012) Import and spread of Panton-Valentine Leukocidin-positive Staphylococcus aureus through nasal carriage and skin infections in travelers returning from the tropics and subtropics Clinical Infectious Diseases 54:483-92
3. Zanger P, Nurjadi D, Vath B, Kremsner PG (2011) Persistent nasal carriage of Staphylococcus aureus is associated with deficient induction of human beta-defensin 3 after sterile wounding of healthy skin in vivo. Infections and Immunity 79(7):2658-62
4. 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 200:1907-15