Research in the Sheedlo lab is focused on defining the mechanisms that govern interactions at the host-pathogen interface. Specifically, we are interested in using cryogenic electron microscopy to generate a framework for understanding how toxins, virulence factors, and delivery systems work. We are currently interested in two such systems from Gram-positive pathogen, Clostridioides difficile. The first is a toxin known as the Clostridioides difficile transferase (CDT) or binary toxin. Although CDT is not needed to evoke the pathology associated with disease, it has been linked to strains that produce severe symptoms and present a higher incidence of infection recurrence. The second system is a putative type four secretion system found within the C. difficile genome. At present, little is known about how these type four secretion systems work or the role that they play during infection. Ultimately, our aim is to understand how both CDT and the type four secretion system contribute to the pathology induced upon C. difficile infection.
