Biochemical and structural characterization of bacterial type III secretion system components

Harmful bacteria are becoming much more resistant to the currently available antibiotics, a situation that poses a serious threat to public health. The development of new and more effective ways of protecting against these increasingly dangerous (and antibiotic resistant) microbes requires a thorough understanding of the molecular mechanisms through which they cause disease. The bacterial type III secretion system (TTSS) is a complex mechanism that controls how bacterial proteins are transfered into human cells, a process that is essential to the disease-causing capabilities of a large number of pathogens, including Salmonella and pathogenic E.coli. Although many components of the TTSS have been identified, exactly how this secretion system is assembled and how virulence proteins (toxins) are delivered into target cells remains poorly understood. With support from a 2002 MSFHR Trainee Award, Calvin Yip successfully described the first high resolution structure of an extracellular component of the TTSS. Now funded for a second time, he is working to further characterize its structure and function. This work will help answer fundamental questions about the biochemical and structural characterization of TTSS, and may facilitate the design of new classes of drugs to combat a broad range of infectious agents.