STAPHEX II: Untersuchung des Exits von Staphylococcus aureus aus Makrophagen

15.01.2023 bis 14.01.2027

The SPP 2225 explores the spectrum of strategies that are employed by intracellularly living bacterial, parasitic and fungal pathogens to exit the enveloping host cell. Host cell exit follows an actively orchestrated programme that has evolved during host-pathogen co-evolution and relies on the dynamic interplay between host and microbial factors. At least three distinct pathways of host cell exit have convergently evolved among the diverse groups of intracellular pathogens, (1) the initiation of programmed cell death, (2) the active lytic destruction of the host cell, and (3) the membrane-dependent exit without host cell lysis.
It is the goal of the SPP 2225 to dissect the molecular mechanisms that trigger, regulate, and synchronize pathogen exit in order to gain in-depth knowledge of this important and yet under-investigated step of human pathogenesis and to unveil the link between exit strategy and disease progression. We aim to particularly investigate the following aspects:
• The sequential steps of pathogen-specific host cell exit pathways
• The link between exit pathway and host cell specificity
• The signalling pathways triggering and mediating host cell exit
• The key molecular mediators, regulators and effectors of host cell exit
We expect that knowledge gained by the SPP 2225 will not only deepen our understanding in the fundamental processes of infection by human pathogens, but will additionally advance our knowledge about tissue inflammation and infection-induced organ dysfunction. Results obtained by the SPP 2225 will eventually lead to the identification of novel interventional targets to combat human infectious diseases worldwide, which is especially important in view of the increasing microbial resistance to current treatment regimes.