Identification of synthetic chemical compound inhibitors of Pseudomonas aeruginosa protein synthesis and the development of lead series

Author

Stephanie O. Palmer, The University of Texas Rio Grande Valley

Date of Award

5-2016

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

First Advisor

Dr. James Bullard

Second Advisor

Dr. Evangelia Kotsikorou

Third Advisor

Dr. Megan Keniry

Abstract

Pseudomonas aeruginosa is a ubiquitous Gram-negative bacteria and a primary cause of nosocomial infections. An aminoacylation/translation (A/T) assay was developed using P. aeruginosa components to perform poly(U) mRNA directed protein synthesis. Using scintillation proximity assay (SPA) technology a high-throughput screening (HTS) platform was developed. A synthetic chemical compound library (>900) was screened, 36 hit compounds were identified and molecular targets were determined. Compounds were analyzed for enzymatic inhibition (IC50) and inhibition of bacterial cultures (MIC). Time-kill studies determined bacterial growth to be bacteriostatic or bactericidal in the presence of inhibitor. Mechanism of action, effects on eukaryotic cytosolic and mitochondrial protein synthesis were determined. Cytotoxicity using a mammalian cell line and global mode of inhibition was determined. One compound was evaluated for the ability to generate spontaneous resistant mutants or develop resistance after serial passage.

Comments

Copyright 2016 Stephanie O. Palmer. All Rights Reserved.

https://www.proquest.com/dissertations-theses/identification-synthetic-chemical-compound/docview/1810998699/se-2?accountid=7119

Recommended Citation

Palmer, Stephanie O., "Identification of synthetic chemical compound inhibitors of Pseudomonas aeruginosa protein synthesis and the development of lead series" (2016). Theses and Dissertations. 78.
https://scholarworks.utrgv.edu/etd/78