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How bacterial pathogens establish chronic infection

Type IV secretion (T4S) systems enable pathogenic bacteria to establish long lasting infection of the host eventually leading to chronic disease. Better understanding of the molecular mechanisms underlying long-term bacterium-host interaction is essential for the development of new medicinal products against infectious diseases.

Infectious diseases of bacterial origin are a growing problem in today's society. The reasons for this are the increasing emergence of antibiotic resistant organisms, the reduction in immune defenses with age, and the rapid spread of new pathogens as a result of globalization. We have to understand the underlying molecular mechanisms in order to conceive new therapeutic approaches to pathogenic bacteria. Bacterial pathogens can survive for long periods in human hosts where they give rise to a chronic course of infection. This bacterial property, known as persistence, is still little understood.

Type IV secretion systems inject effector proteins into host cells
The goal of the work in our laboratory is to investigate chronic bacterial infections at the molecular and cellular level. Our focus is on bacterial effector proteins injected into the host cells by type IV secretion systems. These effector proteins alter targeted signaling pathways and the physiology of the host cells, which facilitate bacterial survive in the host.

Bartonella and Brucella as modal organisms for type IV secretion
We are studying the closely related pathogens Bartonella and Brucella, which cause chronic bacterial infections of varying severity in humans and animals. Their type IV secretion systems contribute decisively to establishing persistent infection and are therefore particularly suitable for our experiments in cell cultures and animal models.

Starting point for new drugs to combat infectious diseases
As part of the Swiss-wide systems biology initiative SystemsX.ch, we identify the cellular interaction partners of bacterial effector proteins. In addition, we characterize all the other host cell proteins relevant to the development of infection and test their suitability as starting points for designing new antimicrobial agents to combat chronic bacterial infections.

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