Project 1: “Prerequisites for successful S. aureus nasal colonization: Impact of strain-specific features and of the nasal microenvironment” Prof. Dr. med. K. Becker, Co-investigators Dr med. B. Löffler, PD Dr. med. B. Kahl, Prof. Dr. med. G. Peters Institute of Medical Microbiology Co-investigator Prof. Dr. rer. nat. D.H. Pieper Dept. of Microbial Pathogenesis, Helmholtz Centre for Infection Research Project 4: “Mechanisms of human skin to control the growth of S. aureus” PD Dr. med. R. Gläser Co-investigators Dr. Dr. med. U. Meyer-Hoffert, Prof. Dr. rer. nat. J. Harder Dept. of Dermatology, Allergology and Venerology Publikationen der Mitarbeiter seit 2009: Gläser R, Meyer-Hoffert U, Harder J, Cordes J, Wittersheim M, Kobliakova J, FölsterHolst R, Proksch E, Schröder JM, Schwarz T (2009): The Antimicrobial Protein Psoriasin (S100A7) Is Upregulated in Atopic Dermatitis and after Experimental Skin Barrier Disruption. J Invest Dermatol 129: 641-649 Gläser R, Navid F, Schuller W, Jantschitsch C, Harder J, Schröder JM, Schwarz A, Schwarz T (2009): Ultraviolet-B radiation induces the expression of antimicrobial peptides in human keratinocytes in vitro and in vivo. J Allergy Clin Immunol 123:1117-23 Wu Z, Hansmann B, Meyer-Hoffert U, Gläser R, Schröder JM (2009): Molecular Identification and Expression Analysis of Filaggrin-2, a Member of the S100 Fused-Type Protein Family. PLoS One 4(4):e5227 Kantyka T, Latendorf T, Wiedow O, Bartels J, Gläser R, Dubin G, Schröder JM, Potempa J, Meyer-Hoffert U (2009): Elafin is specifically inactivated by RGPB from Porphyromonas gingivalis by distinct proteolytic cleavage. Biol Chem 390(12): 13131320. Harder J, Dressel S, Wittersheim M, Cordes J, Meyer-Hoffert U, Mrowietz U, FölsterHolst R, Proksch E, Schröder JM, Schwarz T, Gläser R (2010): Enhanced expression and secretion of antimicrobial peptides in atopic dermatitis and after superficial skin injury. J Invest Dermatol;130(5):1355-64. Dressel S, Harder J, Cordes J, Wittersheim M, Meyer-Hoffert U, Sunderkötter C, Gläser R (2010): Differential expression of antimicrobial peptides in margins of chronic wounds. Exp Dermatol 19(7):628-32 Abtin A, Eckhart L, Gläser R, Gmeiner R, Mildner M, Tschachler E (2010): The Antimicrobial Heterodimer S100A8/S100A9 (Calprotectin) Is Upregulated by Bacterial Flagellin in Human Epidermal Keratinocytes. J Invest Dermatol 130(10):2423-30. Simanski M, Dressel S, Gläser R, Harder J (2010): RNase 7 protects healthy skin from Staphylococcus aureus colonization. J Invest Dermatol 130(12):2836-8 Laudien M, Dressel S, Harder J, Gläser R (2011): Differential expression pattern of antimicrobial peptides in nasal mucosa and secretion. Rhinology 49(1):107-11. Garreis F, Gottschalt M, Schlorf T, Gläser R, Harder J, Worlitzsch D, Paulsen FP (2011): Expression and regulation of antimicrobial peptide psoriasin (S100A7) at the ocular surface and in the lacrimal apparatus. Invest Ophthalmol Vis Sci (epub 6 May) Köten B, Becker K, Podschun R, von Eiff C, Harder J, Gläser R (2011): Susceptibility of Staphylococcus aureus bacteremia strains to different epithelial antimicrobial proteins. J Antimicrob Chemother (submitted) M. Simanski, Köten B, Gläser, A. Peschel and J. Harder: Staphylococcus aureus subverts cutaneous defense by d-alanylation of teichoic acids, Exp. Dermatol (submitted) Project 5: “Staphylococcal factors of interaction with antimicrobial peptides and binding partners on epithelial and epidermal surfaces” Prof. Dr. rer. nat. A. Peschel Medical Microbiology and Hygiene Department, Tübingen Prof. Dr. rer. nat. H.G. Sahl Medical Microbiology, Immunology, and Parasitology, Bonn Sass, V., Pag, U., Tossi, A., Bierbaum, G., Sahl, H.G. (2008). Mode of action of human βdefensin 3 (hBD3) against Staphylococcus aureus and transcriptional analysis of responses to defensin challenge. Int. J. Med. Microbiol. 298, 619-633. Antcheva, N., Morgera, F., Creatti, L., Vaccari, L., Pag, U., Pacor, S., Shai, Y., Sahl, H.G, Tossi, A. (2009). Artificial beta-defensin based on a minimal defensin template. Biochem. J. 421, 435-447. Schneider, T. & Sahl, H.G (2010). An oldie but a goodie – cell wall biosynthesis as antibiotic target pathway. Int. J. Med. Microbiol., 300, 161-169. Schneider, T. & Sahl, H.G. (2010). Lipid II and other bactoprenol-bound cell wall precursors as drug targets. Curr. Opin. Investig. 11, 157-164. Sass, V., Schneider, T., Wilmes, M., Tossi, A., Novikova, N., Shamova, O. Sahl., H.G. (2010). Human beta-defensin 3 (hBD3) inhibits staphylococcal cell wall biosynthesis. Infect. Immun., 78:2793-800. Schneider, T., Kruse, T. Wimmer, R., Wiedemann, I. Sass, V., Pag, U., Jansen, R., Nielsen, A.K., Mygind, P.H., Neve, S., Ravn, B., de Maria, L., Sahl, H.G., Kristensen, H.H. (2010). Plectasin, a fungal defensin antibiotic peptide, targets the bacterial cell precursor lipid II. Science 328:1168-1172. Schmitt, P., Wilmes, M., Pugniere, M., Aumelas, A. Bachere, E., Sahl, H.G., Schneider, T., Destoumieux Garzon, D. (2010). Insight into invertebrate defensisn mechanism of action: oyster defensins inhibit peptidoglyca biosynthesis by binding to lipid II; J. Biol. Chem. 285: 29208-29216 Wilmes, M., Cammue, B. P., Sahl, H.G., Thevissen, K. (2011). Antibiotic activities of host defense peptides: more to it than lipid bilayer perturbation. Nat Prod Rep.28:1350-1358 Project 6: “S. aureus extracellular adhesion protein (Eap) and the skin: Pathogenic insights and ensuing strategies for prevention and treatment of cutaneous infection” Prof. Dr. med. M. Herrmann Institute of Medical Microbiology, Homburg Prof. Dr. rer. nat. K.T Preissner Institute of Biochemistry and Pathobiochemistry, Giessen Project 7: “Identification of genetic factors and immunological mechanisms underlying host resistance / susceptibility to S. aureus in a mouse model of infection” E. Medina, PhD Co Investigator: Dr. Oliver Goldmann Infection Immunology Research Group Bisher aus dem Projekt hervorgegangene Publikationen: Ziegler C, Goldmann O, Hobeika E, Geffers R, Peters G, Medina E. The dynamics of T cells during persistent Staphylococcus aureus infection: from antigen-reactivity to in vivo anergy. EMBO Mol Med. 2011; 3(11):652-66 Abel J, Goldmann O, Ziegler C, Höltje C, Smeltzer MS, Cheung AL, Bruhn D, Rohde M, Medina E. Staphylococcus aureus evades the extracellular antimicrobial activity of mast cells by promoting its own uptake. J Innate Immun. 2011; 3(5):495-507 (The Editors' Choice for issue 5/2011) Tuchscherr L, Medina E, Hussain M, Völker W, Heitmann V, Niemann S, Holzinger D, Roth J, Proctor RA, Becker K, Peters G, Löffler B. Staphylococcus aureus phenotype switching: an effective bacterial strategy to escape host immune response and establish a chronic infection. EMBO Mol Med. 2011; 3(3):129-41 Nippe N, Varga G, Holzinger D, Löffler B, Medina E, Becker K, Roth J, Ehrchen JM, Sunderkötter C. Subcutaneous infection with S. aureus in mice reveals association of resistance with influx of neutrophils and Th2 response. J Invest Dermatol. 2011; 131(1):125- 32. von Köckritz-Blickwede M, Konrad S, Foster S, Gessner JE, Medina E. Protective role of complement C5a in an experimental model of Staphylococcus aureus bacteremia. J Innate Immun. 2010; 2(1):87-92. von Köckritz-Blickwede M, Rohde M, Oehmcke S, Miller LS, Cheung AL, Herwald H, Foster S, Medina E. Immunological mechanisms underlying the genetic predisposition to severe Staphylococcus aureus infection in the mouse model. Am J Pathol. 2008; 173(6):1657-68. (Faculty of 1000 Biology: evaluations for von Köckritz-Blickwede M et al Am J Pathol 2008 Dec 173 (6):1657-68 http://www.f1000biology.com/article/id/1157428/evaluation)