Bacterial Pathogenesis and Antibiotic Drug Discovery
AG Rybniker
Research focus
The global emergence of multi-resistant bacteria is a burden on healthcare systems due to increasing morbidity and mortality. To prevent the current trend of further development of resistance to antibiotics, a comprehensive understanding of bacterial pathogenesis is essential. In our group, we work on all relevant aspects of bacterial virulence factors, pathogen-host interactions and the investigation of essential bacterial enzymes and metabolic pathways. We mainly use high-throughput molecular biology methods and our experiments always focus on potential clinical applications in the fight against multi-resistant pathogens. The focus is on multi-resistant tuberculosis pathogens, which are currently spreading rapidly in many European countries, as well as multi-resistant Gram-negative pathogens.
Host cell-based drug screening methods
In addition to the development of new antibiotics, alternative approaches such as anti-virulence and immune-supporting drugs are also needed to close the antibiotic gap that has emerged in recent decades. We have developed a drug-screening platform for Mycobacterium tuberculosis (Mtb) that enables the identification of these three classes of compounds (antibiotics with a new mechanism of action, anti-virulence drugs and immunotherapeutics) in a single approach. Our comprehensive screening approach is based on the lysis of host cells by virulence factors. Using this method, new Mtb-specific antibiotics as well as inhibitors of the ESX-1 secretion system, a major virulence factor of Mtb, have been identified. We will continue to expand this extremely successful approach and transfer it to other pathogens.
Cell death mechanisms in intracellular pathogens
Mtb is a highly successful intracellular pathogen based on its ability to manipulate innate immunity countermeasures of its major host, the human macrophage. Lytic host cell death is essential for bacterial dissemination and represents an important research topic both mechanistically and from a therapeutic perspective. Our aim is to study how Mtb modulates regulated cell death in myeloid cells and to address the functional role of different cell death pathways in Mtb infection.
