In the course of infection, many bacterial, fungal and protozoan pathogens pass through a life-cycle phase during which they parasitize host cells, typically enclosed by membranous vacuoles. While the intracellular life-style provides shelter to these microbes, they eventually need to exit the enveloping cell to ensure life-cycle progression and dissemination. Host cell exit follows an orchestrated and temporally defined programme that relies on the dynamic interplay between host and microbial factors. Three distinct pathways of host cell exit have been postulated, which appear to have convergently evolved among the otherwise highly diverse groups of pathogens: (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. Molecules involved in the exit process are essential for microbial survival and progression of the infection and thus represent important antimicrobial targets.
The SPP 2225 aims at exploring the spectrum of convergently evolved exit pathways employed by bacterial, parasitic and fungal pathogens with relevance for human health. Considered exit types include exit from the host cell, exit from vacuolar compartment as a prerequisite of host cell exit, and exit from a pathogen-containing cyst. It is the goal of the SPP 2225 to dissect the molecular mechanisms that trigger, regulate, mediate, and synchronize the exit programme, and to unveil the link between exit strategy and disease pathogenesis.
In detail, the following aspects are in the focus of SPP 2225:
•The sequential steps of pathogen-specific host cell exit pathways
•The link between exit pathway and host cell specificity
•The endogenous and environmental triggers of host cell exit
•The signalling pathways mediating host cell exit
•The key molecular mediators, regulators and effectors of host cell exit
•The cross-taxa conservation and species-specific variation of host cell exit
Technical tools to address these questions include combinations of high-end imaging techniques, global analyses based on transcriptomics, proteomics and lipidomics, modern genetics methodologies, like genome editing, and BioID or other molecular interaction detection technologies.
The proposals will be evaluated during a review colloquium scheduled for May 4-6, 2020, at Schloss Mickeln in Düsseldorf (https://www.uni-duesseldorf.de/home/universitaet/strukturen/tagungs-und-gaestehaeuser/gaestehaeuser/schloss-mickeln.html). Hotel rooms are reserved for the applicants. For more information, contact the coordination office.
The Priority Programme SPP 2225 coordination office can be contacted at:
For scientific enquiries, please contact the Priority Programme SPP 2225 coordinator:
Prof. Dr. Gabriele Pradel
Division of Cellular and Applied Infection Biology
Institute of Biology 2
RWTH Aachen University
Worringer Weg 1
phone +49 241 80-20848
The elan system can be accessed at:
Questions on the DFG proposal process can be directed to:
Dr. Andreas Strecker
phone +49 228 885-2530
phone +49 228 885-2390