Hier finden Sie uns


Kirrberger Str. Geb.43
66424 Homburg

Kontakt

Rufen Sie einfach an unter

 

+49 06841 1623900 +49 06841 1623900

 

 

 

Research topics

Bacterial adhesion and biofilm formation: Physical processes at interfaces

The interaction of microorganisms with biologic or artificial surfaces is a key factor in disease pathogenesis. The goal of this research project is to use advanced biophysical methods in combination with microbial genetic engineering for the physical modelling of single and consortial bacterial cell processes resulting in substrate colonization. Insights in these phenomena will help to explore new avenues in prevention and treatment of major bacterial infections. The  experimental  approach  is  centered  on  a correlative approach

using conventional adhesion assays, dynamic adhesion assays at defined flow conditions as well as physical determination of surface forces using the SPM. The surface properties of staphylococcal cells will be tightly controlled by use of defined mutants, and surface forces will be analyzed by comparing results obtained with single cells of respective mutants. (Image by P. Jung)

This research project is part of the collaborative research centre 1027 supported by the Deutsche Forschungsgemeinschaft

For further information, please contact P. Jung, K. Jacobs,  and M. Bischoff

 

 

-------------------------------------------------------------------------------------------------------------------------------------

S. aureus extracellular adhesion protein (Eap) and the skin: Pathogenic insights and ensuing strategies for prevention and treatment of cutaneous infection

infections are associated with non-healing wounds, and bacterial products such as "extracellular adhesive protein" (Eap) may be involved in the pathogenesis of skin diseases. Eap provides a broad spectrum of binding activities to skin extracellular matrix and cellular components. It thereby interferes on multiple levels with host defense by inhibiting leukocyte recruitment and neovascularization and by affecting signal transduction. Yet, the underlying pathogenetic mechanisms with particular emphasis on inflammatory skin diseases are not understood. Our project addresses Eap-mediated bacterial colonization as well as explore the anti-inflammatory and anti-proliferative activities of Eap on keratinocytes and tissue cells. The picture shows uptake of S. aureus Eap by HaCaT cells visualized by antiEap antibodies (image by S. Bur).

Functional activities of Eap and Eap analogues in acute and chronic skin wounds are studied. The project relies heavily on the collaboration with the network partners providing genetically characterized clinical strains, skin defense cells, dermal tissue, and animal models of colonization and skin infection. On the other hand, the project itself provides Eap, Eap fragments and analogues, anti-Eap mAb as well as animal models (wound infection model, intravital fluorescence microscopy model) for use in collaborative projects. Our approach allows to unravel Eap-based therapeutic targets essential for wound healing, skin colonization, and chronic inflammatory skin disease.

 

For further information, please contact M. Bischoff and J. Eisenbeis

 

-------------------------------------------------------------------------------------------------------------------------------------

Regulation of carbon metabolism in staphylococci: The impact of catabolite control protein A and related factors on pathogenicity of Staphylococcus aureus and Staphylococcus epidermidis

Carbon catabolism-affecting factors have been shown in many bacteria to influence virulence and pathogenesis. We recently identified the catabolite control protein A (CcpA) in Staphylococcus aureus, which is thought to be the major regulator of carbon catabolite repression (CCR) in Gram-positive bacteria. During the first funding period, we could show that the deletion of this regulator affected carbon metabolism, virulence determinant production, and infectivity of this pathogen. Aim of the second funding period of this project is now the characterization of the regulatory control of this DNA-binding protein in S. aureus, its impact on infections that are frequent in diabetic patients, and its role in persistence within its host. We will also try to identify the transcriptional changes that occur during the early adaptation processes of S. aureus within its host, and we are planning to characterize further carbon metabolism-affecting regulators of this organism, such as CcpE, CodY, and RpiRc. The proposed work will yield detailed insights into metabolic processes that are effective within S. aureus and its host during invasion and persistence, and into regulatory circuits that link carbon metabolism and virulence in this pathogen.

For further information, please contact R. Gaupp and M. Bischoff

 

------------------------------------------------------------------------------------------------------------------------------------

Infection Biology and Epidemiology of Staphylococci and Staphylococcal Diseases in Africa

continues to be a major pathogen causing invasive disease with high associated morbidity and mortality. The pathogen has acquired resistance against virtually all antimicrobials available, and in the recent years, the worldwide emergence of multiresistant S. aureus clones in hospitals and communities has spurred significant concern for local and global health initiatives. In contrast to the ‘classical’ tropical diseases, however, almost nothing is known on the strain phylogeny and prevalence, disease type, and associated morbidity and mortality of infections due to S. aureus in most African countries. This proposal submitted by four sub-Saharan African and five German groups thus focusses on a registry of S. aureus community-acquired disease, on the isolation and characterization of clinical isolates with advanced methods for typing and virulence factor expression, and on GLP-conform long-term isolate handling and scientific database exchange.

Emerging information will allow to associate S. aureus biology with course of disease, and thus provide a basis for future rational multifaceted interventions including diagnostics, therapy, and preventive measures tailored to the resources and requirements of sub-Saharan Africa. Moreover, the applied academic exchange and workshop program as well as case ascertainment and isolate characterization based on shared criteria and techniques will foster the combat against this pathogen in African countries as well as in Germany.

Members of the Study Consortium

Further information on the homepage of the project http://www.african-german-staph.net/

For additional information, please contact M. Bischoff and M. Herrmann (consortium speaker)

 

The Health Research Center Manhica, Mozambique

This project has been granted a multicenter research grant by a special program of the Deutsche Forschungsgemeinschaft ‘German-African Cooperative Projects in Infectious Diseases’ (PAK 296)

 

 

-----------------------------------------------------------------------------------------------------------------------------------------

Non-zoonotic and zoonotic MRSA: Factors promoting colonization and defence resistance in humans and animals

A number of recent genetic studies have greatly contributed to our understanding that LA-MRSA of the clonal complex (CC) 398 most likely originated from human MSSA ancestors, and that genetic adaptations such as the acquisition of tetracycline resistance determinants and the loss of a number of immunomodulatory and adhesive factors likely contributed to the successful spread of this lineage in livestock. However, these studies do only poorly explain why CC398 MRSA derivatives are such successful colonizers of pigs, and why some of them are readily reintroduced into and spread within the human population, where they may cause severe infections, despite of the fact that most of these isolates lost a number of important virulence determinants. To gain some insights into the molecular mechanisms that contribute to the colonization abilities of CC398 MRSA isolates, we are determining and comparing the transcriptional activities of selected regulatory factors/virulence determinants and/or transcriptomes of CC398 MRSA colonizing human and porcine-derived skin- and nasal epithelia. We hope that these studies will allow us to identify regulatory and/or functional mechanisms that contribute to the ability of CC398 isolates to cross the species barrier and to successfully colonize a multitude of species.

This research is supported by a Network Programme of the Federal Minister of Education and Research "MedVetStaph"

For further information, please contact J. Eisenbeis and M. Bischoff

 

 

Outbreak investigations and epidemiology of Clostridium difficile in Germany and abroad

 

The bacterium Clostridium difficile (C. difficile) is the major causal agent for nosocomial and antibiotic-associated diarrheal disease, and a common cause of outbrakes in the hospital setting, but also in out-patient facilities, such as rehabilitation centers. In order support the UKS and other institutions in their outbreak investigation, and to evaluate if an outbreak is currently ongoing, which strains are involved, and if the hygiene measures taken are effective, the Clostridium difficile Advisory Laboratory, which is part of the IMMH, provides antibiotic resistance testing- and modern typing capabilities, such ribotyping and multilocus variable-number tandem-repeat analysis (MLVA). 

 

The epidemiology of pathogens such as C. difficile is always in flux. New strains may be imported from abroad, and novel, more virulent strains may emerge. For an active surveillance it is essential to detect strains of higher epidemiological importance, such as ribotype 027 isolates, which are associated with an increased virulence potential. In collaboration with several national and international institutions, the Clostridium difficile Advisory Laboratory genetically characterizes strains that are send in by other laboratories German wide, and determines the virulence potential of these strains by a number of phenotypic assays.

 

Work of the Clostridium difficile Advisory Laboratory is funded by the Robert Koch Institute (RKI)

 

For further information, please contact F. Berger and B. Gärtner