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Typhoid toxin: a window into the unique biology of Salmonella typhi

Wednesday, June 25, 2014

Speaker

Jorge E. Galán, Ph.D., D.V.M.
Lucille B. Markey Professor of Microbiology, Chair
Yale University School of Medicine

Dr. Galán has made numerous contributions to the field of bacterial pathogenesis. He has pioneered the study of the cell biology of infection and the mechanisms of pathogenesis of the enteric pathogens Salmonella spp. and Campylobacter jejuni. These two pathogens account for the majority of cases of infectious diarrhea worldwide, leading to an estimated two million deaths per year. His work has led to the understanding of mechanisms by which these pathogens enter and replicate within mammalian cells and has established paradigms applicable to other pathogens.

Summary

Dr. Galán’s studies have led to the identification of the first pathogenicity island in Salmonella and the discovery and characterization of a type III protein secretion system (TTSS) in these bacteria, a specialized organelle that mediates the transfer of bacterial proteins into host cells. In a joint effort with Dr. Aizawa, his laboratory discovered the “needle complex”, a bacterial organelle that constitutes the core component of TTSSs. His work on TTSSs has illuminated several aspects of TTSS function, including its three dimensional structure and assembly, the role of specific chaperones as well as the mechanism of substrate recognition, unfolding, and sorting. He has also pioneered the study and characterization of bacterial effector proteins delivered by TTSSs and his work has led to the identification and characterization of a several bacterial proteins that mimic the function of eukaryotic cell proteins. He has also pioneered the use of the TTSS as an antigen delivery system for vaccine development. His laboratory has also made seminal discoveries in the field of bacterial toxinology, including the discovery of “typhoid toxin”, a unique toxin produced by Salmonella typhi, the cause of typhoid fever, and the discovery of the mechanism of action of the Cytolethal Distending Toxin (CDT), which is produced by many important bacterial pathogens.


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