Author ORCID Identifier
0000000270414570
Date of Award
12-2022
Degree Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Chemistry
First Advisor
Giovanni Gadda
Abstract
Pseudomonas aeruginosa is a ubiquitous single-flagellated motile gram-negative bacterium found in soils, water bodies, plants, and animal tissues. It causes life-threatening nosocomial infections in patients and is responsible for over 51,000 healthcare-associated infections, with ~ 440 annual death reports in the USA only. In recent years, there has been an increased prevalence of P. aeruginosa multidrug-resistant strains creating the need for alternative therapeutic development against P. aeruginosa infections. However, none of the current treatment regimens focuses on eliminating enzymes of primary and secondary metabolic pathways. Targeting essential metabolic pathways makes it possible to inhibit bacterial growth by inhibiting relevant biochemical enzymes required for P. aeruginosa metabolism. Flavoenzymes catalyze a broad spectrum of reactions. The ability of the flavin cofactor to participate in diverse reaction mechanisms makes flavoenzymes prevalent in multiple metabolic pathways, thus, serving as good therapeutic targets. Unfortunately, several P. aeruginosa genes remain annotated as hypothetical proteins due to the slow rate of biochemical characterization of gene products. To fully understand the mechanisms of action of essential flavoenzymes, the enzymes need extensive biochemical, mechanistic, and kinetic characterization. This study focuses on the characterization of three critical P. aeruginosa PAO1 metabolic enzymes, namely D-arginine dehydrogenase (PaDADH), NADH:quinone oxidoreductase (PaNQO), and D-2-Hydroxyglutarate dehydrogenase (PaD2HGDH). These enzymes’ kinetic and biochemical properties are investigated and discussed with the aim of alternative therapeutic development against P. aeruginosa strain PAO1.
Recommended Citation
Quaye, Joanna, "Biochemical Characterization of Selected Flavin-Dependent Metabolic Enzymes of Pseudomonas aeruginosa PAO1 Toward Alternative Therapeutic Development." Dissertation, Georgia State University, 2022.
https://scholarworks.gsu.edu/chemistry_diss/238
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