Mode of action of the serine protease autotransporter EspP from enterohemorrhagic Escherichia coli

• Applicant: Professor Dr. Jens Brockmeyer
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2011 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 210149347

The infection with enterohemorrhagic Escherichia coli (EHEC) can lead to severe diseases such as hemorrhagic colitis and the life-threatening hemolytic uremic syndrome (HUS) which is characterized by thrombocytopenia, hemolytic anemia and acute renal failure. While pathogenesis of EHEC infections is not understood in detail it is believed that besides Shiga toxins additional factors such as the serine protease autotransporter EspP contribute to EHEC virulence. We demonstrated in our previous work that EspP occurs in at least four subtypes (EspPα-EspPδ) which display substantial differences on structural and functional level. Interestingly, we found that highly virulent EHEC serotypes exclusively harbor the most active subtype EspPα and were able to identify those modifications that underlie functional differences. On functional level, it was demonstrated that EspPα degrades substrates involved in hemostasis and the complement factors C3 and C5. To understand the molecular and cellular mode of action of EspPα in more detail, we aim in this project to: (1) Identify the physiological relevant substrates of EspPα on proteome-wide level; (2) analyze the influence of factors of the host environment on expression and functionality of EspPα; (3) investigate the capability of EspPα to bind to cellular surfaces and (4) elucidate structure-functional relationships in comparison to other EHEC serine protease autotransporters such as EspI. These data will illuminate the role of EspPα during EHEC infection.

• DFG Programme: Research Grants