Date of Award:
Doctor of Philosophy (PhD)
Chemistry and Biochemistry
Nicholas E. Dickenson
Nicholas E. Dickenson
Joan M. Hevel
Many human bacterial pathogens cause infection by relying on a type-III secretion system (T3SS). A type-III secretion system creates a protein nano-machine that resembles a hypodermic needle that allows the bacteria to penetrate a host cell and inject proteins that cause the host cell to take in the bacteria. The bacteria that have invaded the host are then able to replicate and cause increased infection. A T3SS is essential to many pathogens’ ability to cause infection, the importance of the T3SS forces bacteria to control the assembly of the T3SS so that it can be utilized during infection. Due to the immense global burden and emergence of antibiotic-resistant strains, this work focuses on the human pathogen Shigella flexneri and the regulation of its T3SS. While much is known about how Shigella controls the expression of the genes that produce the T3SS, little is known about how the needle-like structure is regulated after it has been formed. A recent study found many T3SS proteins to be modified after expression including Spa47, which is an essential protein in the T3SS. To understand how this modification might affect the activity of Spa47, amino acid mutations were used to mimic the protein modifications. These mutations were found to severely inhibit the activity of Spa47 and the ability of Shigella to cause infection. We then attempted to identify the proteins responsible for these modifications to Spa47 but were unsuccessful. Through these studies, a protein that disrupted the ability of Shigella to cause an infection was found, called BipA.
It was observed that BipA causes inhibition of the ability of Shigella to express T3SS genes. This is a novel regulation pathway in Shigella. Overall, this work provides insights and breaks new ground in understanding how Shigella regulates its T3SS and provides a step toward new targets for therapeutics to fight Shigella infections
Hardy, Koleton D., "Exploring Mechanisms of Native Regulation in the Shigella Type-III Secretion System" (2023). All Graduate Theses and Dissertations, Fall 2023 to Present. 98.
Available for download on Friday, December 01, 2028
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