Generalized bacterial infections remain a serious problem. If they take a severe course, they have a mortality rate of around 50%, and they are the most common cause of death in patients in intensive care today. But even when their outcome is favourable, they are a large burden for the patients and the health-care system, due to prolonged hospitalization and associated high costs. The causal treatment options for severe generalized bacterial infections are limited. Due to the rapid spread of bacteria with resistance to (almost) all antibiotics, the treatment options available further lose efficacy, which gives rise to serious concern. Generalized bacterial infections are a complex interplay between bacterial virulence factors and the hostís defence systems. To better understand the multi-facetted interactions between pathogen and host, an interdisciplinary effort of researchers studying the microorganisms and those focussing on the defence mechanisms is required. However, these researchers traditionally work in different scientific communities. To overcome these limitations, scientists from nine disciplines are joining forces in this Graduate School. Their aim is to increase our knowledge about the molecular mechanisms of pathogenesis, to improve the diagnostics, and in the long run to design new strategies ort he prevention and treatment of generalized bacterial infections. Thus, the research and teaching programs of the Graduate School constitute a scientific environment which encourages graduate students to develop an integrated approach to complex biomedical problems, and to train their teamwork and social skills.

The projects of the current funding period (2007-2012) are focussed on two main topics.

D: Virulence factors in sepsis-associated microorganisms

Please click here to get more information about projects D1 - D7

E: Immunological risk factors and mechanisms of protection in generalized bacterial infections

Please click here to get more information about projects E1 - E7

The projects of the first funding period (2003-2006) were focussed on three main topics.

A: Staphylococcus aureus

The Gram-positive bacterium Staphylococcus aureus exists in many individuals as a harmless commensal, but it also causes a variety of infections ranging from superficial abcesses, osteomyelits, endocarditis, toxic shock syndrome to sepsis. Due to its ubiquity and ability to survive outside the host, Staphylococcus aureus infections are highly prevalent both in the community and in hospital settings. During the last years the therapy of Staphylococcus aureus infections has become even more difficult because of the emergence of drug-resistant staphylococci. For this reason new strategies for the prevention and treatment of these infections are urgently needed.

Please click here to get more information about projects A

B: Polymicrobial peritoneal sepsis

The murine model of the colon ascencens stent peritonitis (CASP) closely mimics the situation of a patient with sepsis due to anastomosis failure after major abdominal surgery. A stent is inserted into the colon wall, leading to fecal leakage into the peritoneal cavity and polymicrobial sepsis. In this model the essential factors causing disease can be identified with the help of knock-out technology and by experimental interference with the immune response.

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C: Immunological risk factors and mechanisms of protection

The individual risk of developing a generalized bacterial infection as well as the outcome of such an adverse event varies greatly. Clinical studies aim at the characterization of patterns of risk factors and at the reduction of the risk of serious infection, which is associated with major surgery. Experimental manipulation of the immune system prior to a bacterial challenge in an animal model may further elucidate mechanisms of protection which could be developed into a strategy of sepsis prevention.

Please click here to get more information about projects C