The Development of Screening Platforms to Identify Novel Anti-Infectives that Inhibit Protein Synthesis in Pseudomonas aeruginosa

Author

Casey Anne Hughes, The University of Texas Rio Grande Valley

Date of Award

5-2019

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

Dr. James Bullard

Second Advisor

Dr. Frank Dean

Third Advisor

Dr. Megan Keniry

Abstract

Pseudomonas aeruginosa, a Gram-negative opportunistic pathogen, is a leading cause of nosocomial infections and is becoming increasingly antibiotic resistant. Aminoacyl-tRNA synthetases (aaRSs) catalyze the covalent attachment of amino acids to their cognate tRNAs and serve as validated targets for the development of new anti-infectives. In P. aeruginosa, the genome contains two genes (tyrS and tyrZ) which encode two distinct TyrRS enzymes. The genes encoding both P. aeruginosa TyrRS-Z and TyrRS-S were cloned, overexpressed in E. coli cells, and purified to homogeneity. Both forms of TyrRS were active in aminoacylation and were developed into screening platforms using scintillation proximity assay (SPA) technology. Using this assay, a chemical compound library was screened to detect compounds with the ability to inhibit the function of TyrRS. A number of inhibitory compounds were confirmed and characterized for the ability to inhibit the enzymatic activity (IC50) of both forms of TyrRS.

Comments

Copyright 2019 Casey Anne Hughes. All Rights Reserved.

https://go.openathens.net/redirector/utrgv.edu?url=https://www.proquest.com/dissertations-theses/development-screening-platforms-identify-novel/docview/2245807045/se-2?accountid=7119

Recommended Citation

Hughes, Casey Anne, "The Development of Screening Platforms to Identify Novel Anti-Infectives that Inhibit Protein Synthesis in Pseudomonas aeruginosa" (2019). Theses and Dissertations. 479.
https://scholarworks.utrgv.edu/etd/479