Dr. Raz Zarivach

2005 Research Trainee Award, Post-Doctoral Fellow

Structural and biochemical analysis of the essential type III secretion system ATPase from Gram-negative pathogenic bacteria

Infection by gram-negative bacteria is a growing threat to humans, animals and plants. The severity of disease and death rate associated with these infections continues to grow because of the increase in antibiotic-resistant strains of these bacteria, including strains of Yersinia, Shigella, Salmonella, Pseudomonas, Chlamydia and enteropathogenic Escherichia coli (EPEC). In several of these organisms, disease-causing properties are dependent upon a type III secretion system (T3SS). The T3SS is a complex of more than 20 unique protein components structured into a syringe-like apparatus, which delivers the virulence factors (toxins) from the bacteria directly into the host cells. A key component for toxin insertion is the activity of a type III ATPase, an enzyme that provides the energy for this process and acts as a gatekeeper on the bacterial inner membrane. Dr. Raz Zarivach’s goal is to determine the first three-dimensional molecular structure of this type III ATPase and further understand its mechanisms and role in virulence. He hopes his work will lead to the design of new drugs that will inhibit this secretion system and protect against these common disease-causing bacteria. Completed award term, April 2008

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