SPP 2225:  Exit strategies of intracellular pathogens

• Subject Area: Medicine ; Biology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 422048538

The priority programme SPP 2225 is an interdisciplinary consortium of microbiologists and infection researchers exploring the spectrum of strategies that are employed by intracellular 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 cell and microbial factors. At least three distinct pathways of host cell exit have convergently evolved among the diverse groups of intracellular pathogens, (1) initiation of programmed cell death, (2) active lytic destruction of the host cell, and (3) membrane-dependent exit without host cell lysis. It is the goal of SPP 2225 to dissect the molecular mechanisms that trigger, regulate, and synchronize pathogen exit and to discover the sequential steps of host cell exit as well as the link between exit pathway and host cell specificity. The breadth of pathogens represented in the SPP 2225 projects allows to compare strategies, find parallels and draw conclusions on universal mechanisms of host cell exit as well as to identify species- or tissue-specific variations of exit pathways. In the second funding period of the SPP 2225, we will apply the data collected so far, as well as the molecular techniques and genetic tools that have been developed during the first funding period, to expand our know-how of the host cell exit mechanisms and to unveil the link between exit strategy and disease progression. Knowledge gained by SPP 2225 will not only deepen insights into the fundamental processes of infection by human pathogens, but will additionally advance our understanding of 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. Various coordination measures have been implemented to enable networking among the scientists of the SPP 2225 consortium, to strengthen the visibility of the SPP 2225 and to promote the training of early career researchers. The strategic concept includes workshops and symposia as well as two technical platforms in addition to network and start-up funds and gender equality as well as public relation measures.

• DFG Programme: Priority Programmes
• International Connection: China

Projects

• Bacterial and host factors governing enterocyte exit of Salmonella (Applicant Hornef, Mathias Walter )
• Characterization of host and bacterial factors affecting the exit of uropathogenic Escherichia coli from intracellular bacterial communities in bladder epithelial cells (Applicants Dobrindt, Ulrich ;  Rescher, Ursula )
• Coordination Funds (Applicant Pradel, Gabriele )
• Deciphering the molecular mechanisms underlying host cell exit of Orientia tsutsugamushi (Applicant Keller, Christian )
• Deciphering the role of spingolipids in bacterial egress (Applicant Heuer, Dagmar )
• Egress mechanisms of Coxiella burnetii (Applicant Lührmann, Anja )
• Escaping the Salmonella-containing vacuole – Role of flagella-mediated damage, cytosolic motility, and host cell apoptosis in exit and transmission of Salmonella (Applicants Erhardt, Marc ;  Hensel, Michael )
• Exit of Mycobacterium avium from granuloma macrophages (Applicant Henneke, Philipp )
• Exit of Plasmodium gametes from red blood cells (Applicant Frischknecht, Friedrich )
• Function of Legionella pneumophila phospholipases in vacuole and host egress (Applicant Flieger, Antje )
• Identification and characterization of novel factors mediating Plasmodium falciparum egress from the red blood cell (Applicant Gilberger, Tim-Wolf )
• Inhibiting Fatty Acid Activation to Induce Phagosome Escape and Enhance Mycobacteria Clearance (Applicant Barisch, Caroline )
• Inside out – The role of mycobacterial ESX secretion systems in phagosome escape (Applicant Gutsmann, Thomas )
• Integrated Proteomics and Lipidomics Platform (Applicants Bindila, Ph.D., Laura ;  Distler, Ute )
• Investigating mechanisms of chromosome segregation during the exit of male Plasmodium gametes. (Applicant Hentzschel, Franziska )
• Mechanisms of Plasmodium departure from the liver infection stage (Applicant Ingmundson, Alyssa )
• Molecular and cellular characterization of cell death pathways involved in Leishmania host cell exit and cell-to-cell transfer (Applicants Müller, Andreas ;  van Zandbergen, Ger )
• Plasmodium Escape from Protective Shells: Species- and Stage-Specific Functions of SERA Cysteine Proteases in Egress from Oocysts and Erythrocytes (Applicant Matuschewski, Kai )
• Plasmodium SNARE proteins in exoneme discharge and merozoite egress (Applicant Matz, Joachim Michael )
• STAPHEX II: Dissecting Staphylococcus aureus macrophage exit (Applicants Weber, Ph.D., Alexander ;  Wolz, Christiane )
• Strategies of Candida albicans and Candida glabrata to exit from macrophages (Applicants Brunke, Sascha ;  Hube, Bernhard )
• The ejectosome: Deciphering its proteome (Applicant Hagedorn, Monica )
• The function and mechanism of cGMP signaling during egress and reactivation of Toxoplasma bradyzoites (Applicant Gupta, Nishith )
• The iBiOs platform for advanced live-cell imaging, ultrastructural analyses and correlative light and electron microscopy in SPP 2225 (Applicants Hensel, Michael ;  Psathaki, Olympia-Ekaterini )
• The role of the Gliding-Initiation-Complex during host cell egress of Toxoplasma gondii (Applicants Jimenez Ruiz, Ph.D., Elena ;  Meißner, Markus )
• Tunneling Nanotubes (TNTs): An Export/Import Strategy for Chlamydia via direct Cell-to-Cell Communication (Applicant Knittler, Michael R. )
• Vesicle dynamics during the egress of malaria gametocytes from the red blood cell (Applicant Pradel, Gabriele )

• Spokesperson: Professorin Dr. Gabriele Pradel