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We are interested in the pathogenesis of staphylococcal infections, mainly focussing on implant-associated infections. Infections occurring after implantation of medical devices (e.g. prosthetic joints, central venous catheters, artificial heart valves) are a major cause of the ever increasing number of nosocomial infections. In Germany alone up to 100.000 infections per year are observed, significantly contributing to in-hospital morbidity and mortality.
Pathogens most frequently isolated during device-related infections are staphylococci, especially Staphylococcus epidermidis and Staphylococcus aureus. Both species organize multilayered bacterial consortia termed biofilms on artificial surfaces. Biofilm formation contributes to S. epidermidis and S. aureus pathogensis by protecting the bacteria from effector mechanisms of the host innate immune system and increasing resistance against antibiotics. By addressing molecular mechanisms involved in staphylococcal biofilm formation a future goal is to identify novel means to combat devastating staphylococcal infections.
Projects are funded by the Deutsche Forschungsgemeinschaft (SFB 470, TP C10; Ro2413/3-1), the ENDO-Stiftung Hamburg, and the ARGUS-Stiftung.
| Position | Name | Phone | Fax | |
|---|---|---|---|---|
| Group leader | PD Dr. med. H. Rohde | (9)52143 | rohde@uke.de | |
| Graduate student | Dipl. Biol. M. Busch | 52152 | m.busch@uke.de | |
| Graduate student | H. Büttner | henning.buettner@stud.uke.de | ||
| Graduate student | R. Decker | 52152 | rahel.decker@stud.uke.de | |
| RA | Dr. rer. nat. M. Kotasinska | 52151 | 53250 | m.kotasinska@uke.de |
| MTA | G. Kroll | 52152 | g.kroll@uke.de | |
| RA | Dr. rer. nat. N. Schommer | 52151 | 53250 | |
| Graduate student | L. Stalling | 52152 | l.stalling@stud.uke.de |
Biofilm formation is a two step process including adherence of the bacteria to the surface to be colonized and subsequent assembly of a multi layered biofilm architecture. The latter phase depends on the expression of intercellular adhesins, stabilizing the biofilm consortium. We are currently interested in factors which functionally contribute to bacterial cell aggregation. By using genetic, biochemical and immunological approaches our focus lies on the analysis of a polysaccharide intercellular adhesin (PIA) which forms a complex extracellular matrix integrating staphylococci into the biofilm. In addition, intercellular protein adhesins like the accumulation associated protein (Aap) are substantially involved in biofilm formation. We have focused our present studies on Aap and additional cell surface associated proteins, aiming at elucidating molecular determinants contributing to their intercellular adhesive properties.
Fig. 1: Schematic representation of Staphylococcus epidermidis biofilm formation. Biofilms are formed in two pahese (primary attachment and accumulation). Both phases involve specific bacterial factors, e.g. surface proteins interacting wit host extracellular matrix proteins and intercellular adhesins.
Biofilm formation is a key virulence mechanism involved in S. epidermidis colonization of artificial (e.g. catheter) and natural (e.g. cardiac valve) surfaces. By using defined S. epidermidis mutants and purified cell surface components we address the question how specific bacterial factors contribute to interactions of S. epidermidis with host structures. We are interested in defining mechanisms involved in reduced susceptibility of S. epidermidis biofilms against uptake by host macrophages. Specifically, we are aiming at elucidating intercellular macrophage events that are associated with failure of phagocytes to eliminate S. epidermidis organized in a biofilm.
In addition, by using cell culture models for endovascular infections we focus on dynamics of S. epidermidis interactions with host endothelium structures which are thought to contribute to endocarditis pathogenesis. Specifically, were we ask how defined S. epidermidis surface proteins interact with host extracellular matrix structures, e.g. fibronectin.
Both, Staphylococcus epidermidis and Staphylococcus aureus belong to the normal human skin flora. Consequently, staphyloccal infections are often endogenous. By analysis of staphylococcal populations from natural environments (e.g. the nose) and infections (e.g. catheter-related blood stream infections) we try to identify markers for increased invasive potential of defined staphylococcal clones. To this end, we apply molecular typing methods (pulsed field gel electrophoresis PFGE, multi locus sequence typing MLST, spa-typing) to characterize collections of staphylococcal isolates from defined isolation sites and search fro the presence of specific virulence associated gene patterns. In addition, we are interested in the development and validation of novel methods (for example by using MALDI-TOF MS) for rapid identification and characterization of clinical Staphylococcus epidermidis and Staphylococcus aureus isolates. In addition, we address molecular epidemiology of resistance mechanisms against antibiotics.
These studies could refine microbiologic diagnostic procedures, optimize antibiotic therapy strategies as well as identify suitable targets for vaccine development.
Christner M, Franke GC, Schommer NN, Wendt U, Wegert K, Pehle P, Kroll G, Schulze C, Buck F, Mack D, Aepfelbacher M, Rohde H.
The giant extracellular matrix-binding protein of Staphylococcus epidermidis mediates biofilm accumulation and attachment to fibronectin.
Mol Microbiol. 2010 Jan;75(1):187-207. Epub 2009 Nov 25.
Rohde H, Frankenberger S, Zähringer U, Mack D.
Structure, function and contribution of polysaccharide intercellular adhesin (PIA) to Staphylococcus epidermidis biofilm formation and pathogenesis of biomaterial-associated infections.
Eur J Cell Biol. 2009 Nov 12. [Epub ahead of print]
Sbarra MS, Arciola CR, Di Poto A, Saino E, Rohde H, Speziale P, Visai L.
The photodynamic effect of tetra-substituted N-methyl-pyridyl-porphine combined with the action of vancomycin or host defense mechanisms disrupts Staphylococcus epidermidis biofilms.
Int J Artif Organs. 2009 Sep;32(9):574-83.
Harris LG, Bexfield A, Nigam Y, Rohde H, Ratcliffe NA, Mack D.
Disruption of Staphylococcus epidermidis biofilms by medicinal maggot Lucilia sericata excretions/secretions.
Int J Artif Organs. 2009 Oct 24.
Jaeger S, Jonas B, Pfanzelt D, Horstkotte MA, Rohde H, Mack D, Knobloch JK.
Regulation of biofilm formation by sB is a common mechanism in Staphylococcus epidermidis and is not mediated by transcriptional regulation of sarA.
Int J Artif Organs. 2009 Oct 24.
Fredheim EG, Klingenberg C, Rohde H, Frankenberger S, Gaustad P, Flægstad T, Sollid JE.
Biofilm formation by Staphylococcus haemolyticus.
J Clin Microbiol. 2009 Jan 14.
Knobloch JK, Von Osten H, Horstkotte MA, Rohde H, Mack D.
Biofilm formation is not necessary for development of quinolone-resistant "persister" cells in an attached Staphylococcus epidermidis population.
Int J Artif Organs. 2008 Sep;31(9):752-60.
Al Laham N, Rohde H, Sander G, Fischer A, Hussain M, Heilmann C, Mack D, Proctor R, Peters G, Becker K, von Eiff C.
Augmented expression of polysaccharide intercellular adhesin in a defined Staphylococcus epidermidis mutant with the small-colony-variant phenotype.
J Bacteriol. 2007 Jun;189(12):4494-501. Epub 2007 Apr 20.
Begun J, Gaiani JM, Rohde H, Mack D, Calderwood SB, Ausubel FM, Sifri CD.
Staphylococcal biofilm exopolysaccharide protects against Caenorhabditis elegans immune defenses.
PLoS Pathog. 2007 Apr;3(4):e57.
Banner MA, Cunniffe JG, Macintosh RL, Foster TJ, Rohde H, Mack D, Hoyes E, Derrick J, Upton M, Handley PS.
Localized tufts of fibrils on Staphylococcus epidermidis NCTC 11047 are comprised of the accumulation-associated protein.
J Bacteriol. 2007 Apr;189(7):2793-804. Epub 2007 Feb 2.
Rohde H, Burandt EC, Siemssen N, Frommelt L, Burdelski C, Wurster S, Scherpe S, Davies AP, Harris LG, Horstkotte MA, Knobloch JK, Ragunath C, Kaplan JB, Mack D.
Polysaccharide intercellular adhesin or protein factors in biofilm accumulation of Staphylococcus epidermidis and Staphylococcus aureus isolated from prosthetic hip and knee joint infections.
Biomaterials. 2007 Mar;28(9):1711-20. Epub 2006 Dec 21.
Rohde H, Burdelski C, Bartscht K, Hussain M, Buck F, Horstkotte MA, Knobloch JK, Heilmann C, Herrmann M, Mack D.
Induction of Staphylococcus epidermidis biofilm formation via proteolytic processing of the accumulation-associated protein by staphylococcal and host proteases.
Mol Microbiol. 2005 Mar;55(6):1883-95.
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