Post-translational modifications as a virulence strategy of diarrheagenic E. coli

With an estimated 1.5 million fatal cases among children and about 2 billion cases total annually, diarrheal diseases are a significant cause for morbidity and mortality worldwide. Enteropathogenic and enterohemorrhagic E. coli (EPEC/EHEC) are two forms of diarrheagenic E. coli that cause these diseases. EPEC provokes potentially fatal infantile diarrhea and EHEC triggers severe diarrhea, which can progress to fatal renal failure. Both pathogens infect epithelial cells of the host intestine. They utilize a sophisticated delivery system, the type III secretion system, to inject specialized effector proteins into the host cytosol. Once translocated, these effectors trigger signaling events to subvert host cell functions and cause disease. However, only little is known about respective host targets and mechanistic details.

Dr. Scholz’s research aims to clarify if and how EPEC/EHEC utilize effectors to interfere with the host posttranslational modification (PTM) machinery and thus with host signaling to promote disease. His research will represent the first comprehensive analysis of the role of PTMs in EPEC/EHEC pathogenesis and will provide new strategies for therapeutic approaches against bacterial pathogens.

Throughout his study, Dr. Scholz plans to pursue identified host targets, elucidate the mechanistic details of this effector-host target interplay and clarify its consequences for pathogenesis. Having already established a highly efficient, reliable and comprehensive screening approach for phosphorylation, a common and pivotal PTM in host signaling, he further plans to employ similar strategies to target also other types of PTMs, such as ubiquitination, and define their role during EPEC/EHEC infection.