Date of Award

12-29-2021

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Applied Science

First Advisor

Shanzhi Wang

Abstract

Bacterial resistance is outpacing the discovery of novel antimicrobials. Therefore, it is essential to look at antimicrobials using novel methods. MTAN is a crucial enzyme for some bacteria such as Helicobacter pylori. Transition state analog inhibitor design and fragment-based drug design are drug design approaches typically used independently, but combining these techniques yields inhibitors that bind tightly and are effective in pM concentrations. We demonstrate the efficacy of the combined techniques by investigating the inhibition of HpMTAN, which is an essential enzyme. Enzyme byproducts can also be effective for causing bacterial cell death, hydrolyzing GsdmD by caspases-1/4/5/11 results in an active N-terminus that causes pore formation by it inserting into the cell membrane. We show that GsdmD N-terminus treated cells have noticeably lower colony counts compared to untreated cells. Lastly, we offer that glucose oxidase conjugated silver nanoparticles have a difference in cell growth upon treatment with as little as 0.667mg/mL. The inhibition of essential enzymes and the utilization of enzyme productions should be further investigated to treat and prevent serious bacterial infections.

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Biochemistry Commons

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