Systemic spread of EHEC virulence by host cell-derived microparticles

• Applicant: Dr. Sebastian Loos
• Subject Area: Pediatric and Adolescent Medicine
• Term: from 2013 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 250089779

Enterohemorrhagic E. coli (EHEC) infection may lead to hemolytic uremic syndrome (HUS) with acute kidney injury and death in both children and adults. The unique virulence factor associated with HUS is Shiga toxin. Previous studies have shown that microparticles are released from blood cells during Escherichia coli O157:H7 infection. These microparticles possess prothrombotic and pro-inflammatory potential. This study will address the specific mechanism by which Shiga toxin reaches its target organs. To this end we will use a well-established mouse model of EHEC infection mimicking certain aspects of HUS and study the importance of microparticles bearing Shiga toxin for the development of full-blown disease. We will attempt to block the transfer of toxin to its target organ cells using various treatments such as a calcium channel blocker, a calpain inhibitor, purinergic receptor inhibitors and anti-Gb3 receptor-antibodies.The overall aim of this project is to investigate if microparticles contain bacterial virulence factors and if these factors can thus be transported systemically to target organs. Ultimately, depending on the findings, the results may offer a novel treatment for this infection.

• DFG Programme: Research Fellowships
• International Connection: Sweden
• Host: Professorin Diana Karpman, Ph.D.