Date of Award

5-2026

Degree Name

Master of Science

Department

Biological Sciences

First Advisor

Benjamin Koestler, Ph.D.

Second Advisor

Silvia Rossbach, Ph.D.

Third Advisor

Karim Essani, Ph.D.

Keywords

Bacterial metabolism, isoleucine metabolism, Shigella amino acid metabolism, Shigella flexneri, Shigella metabolism

Access Setting

Masters Thesis-Open Access

Abstract

Pathogens survive by balancing metabolic demands with environmental challenges that shape their virulence and adaptability. Shigella flexneri, a highly infectious human pathogen responsible for severe diarrheal disease worldwide, utilizes branched-chain amino acid (BCAA) metabolism to withstand stress conditions encountered within the host environment. In this study, we explored the Shigella isoleucine catabolism pathway by knocking out four genes in the S. flexneri isoleucine catabolic pathway (ilvE, fadA, fadD, and acnB) and examining their metabolism and virulence. We found that the ilvE and acnB mutants displayed reduced metabolic activity and smaller plaque size, while the fadD mutant showed decreased invasion. In addition, studies of Tanapoxvirus (TPV), an oncolytic poxvirus that replicates selectively in human colorectal cancer cells, examined the effects of different cell culture conditions on viral propagation. While TPV replicates efficiently in owl monkey kidney (OMK) monolayers, limited surface area hinders large-scale production. Efforts to adapt OMK cells to suspension culture, using shear-protective surfactants such as Pluronic F127, showed cell aggregation and loss of viability. The findings together highlight that both genetic and environmental constraints play central roles in shaping pathogen fitness and potential for biomedical application.

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