Approval of the DFG priority programme "Exit strategies of intracellular pathogens".

  Gabriele Pradel and Mathias Hornef Copyright: Ute Ewodo Prof. Mathias Hornef and Prof. Gabriele Pradel

Prof. Gabriele Pradel has been awarded the DFG priority programme "Exit strategies of intracellular pathogens".

With the announcement of the German Research Foundation on April 1, 2019, the Exit Strategies priority program "Exit strategies of intracellular pathogens" was approved with a funding volume of 6 million euros.

The priority programme is coordinated by Prof. Gabriele Pradel in cooperation with Prof. Mathias Hornef from the University Hospital of RWTH Aachen University (photo), Prof. Antje Flieger (RKI Wernigerode), Prof. Friedrich Frischknecht (UK Heidelberg) and Prof. Georg Häcker (UK Freiburg) as well as scientists from 14 other research locations in Germany.

The results of the priority programme will enrich the basic understanding of microbial pathogenesis and contribute to the identification of new target structures for the control of infectious diseases.

The project, which will start in 2020, focuses on the release of intracellular pathogens from the host cell:

Many bacterial, fungal and protozoan pathogens pass through a life-cycle phase, during which they persist or multiply inside host cells. While the intracellular life-style provides shelter to these microbes, they eventually need to exit the enveloping cell to ensure life-cycle progression. Hence, host cell exit is intimately linked to microbial pathogenesis and crucial for spread of the disease. Initially viewed as a passive process, host cell exit is now seen as an orchestrated and temporally defined programme that has evolved during host-pathogen co-evolution and relies on the dynamic interplay between host and microbial factors. Although host cell exit is an essential step of the infection process, the detailed mechanisms and effector molecules involved remain largely unresolved. Three distinct pathways of host cell exit have been postulated, which appear to have convergently evolved among the otherwise highly diverse groups of bacterial, fungal and protozoan pathogens. These pathways include (i) the initiation of programmed cell death; (ii) the active lytic destruction of the host cell; (iii) the membrane-dependent exit without host cell lysis. Increasing evidence indicates that the majority of intracellular pathogens utilize more than one of these pathways, dependent on life-cycle stage, environmental factors and/or host cell type. Molecules involved in the exit process are essential for microbial survival and spread and thus represent important antimicrobial targets, as illustrated for example by the recent finding that chemical inhibition of plasmodial proteases involved in the egress of the malaria parasite from the enveloping erythrocyte can block disease progression. The priority programme aims at exploring the exit strategies used by important human pathogens, including the infectious agents of such devastating diseases as malaria, tuberculosis and typhoid fever. The priority programme will characterize in great detail the spectrum of convergently evolved exit pathways employed by human bacterial, parasitic and fungal pathogens, dissect the molecular mechanisms that mediate exit from their host cells and cellular compartments, and unveil the link between exit strategy and disease pathogenesis. We expect that findings of the priority programme will substantially advance our fundamental understanding of microbial pathogenesis and identify novel interventional targets to fight infections of worldwide importance.

Information on other DFG projects of Prof. Gabriele Pradel can be found on the GEPRIS page.