Research on Capitol Hill
 

Presenter and Co-Presenter(s)

Jenna BouvangFollow

Expected Graduation Year

2017

College

College of Science

Department

Chemistry and Biochemistry Department

Faculty Mentor

Dr. Nicholas E. Dickenson

Abstract

Shigella flexneri is a bacterial pathogen that causes shigellosis, a severe form of dysentery hallmarked by massive fluid loss and hemorrhaging of the intestines. Though treatable with certain antibiotics, shigellosis presents a worldwide health concern with an estimated 90 million infections and greater than 100,000 deaths annually. Shigella relies on a specialized transport system, called the type three secretion system (T3SS), to directly inject bacterial proteins into human host cells and cause infection. The complex protein machinery of the T3SS is highly conserved among related bacteria including Salmonella (food poisoning), Pseudomonas (lung infections), and Yersinia (plague). The apparatus includes a hollow needle-like structure through which specialized effector proteins are secreted and a sorting platform that resides at the base. We have recently characterized the Shigella sorting platform protein, Spa47, as an ATPase which likely provides the necessary energy for the formation of the T3SS needle and subsequent secretion of bacterial proteins into host cells. In the work presented here, we solved several high-resolution crystal structures of Spa47 which we use to model an activated Spa47 complex and guide the design of key Spa47 mutations, providing the first insight into both the structure and function of what we believe represents the “powerhouse protein” supporting Shigella infection. These findings add to our understanding of how an important class of bacteria cause infection and provide a strong platform for follow-up studies evaluating the regulation of Spa47 oligomerization in vivo as a much needed means of treating and potentially preventing shigellosis and related diseases.

Document Type

Article

Publication Date

2017

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