Title

Synthetic Aptamers and Botanic Compounds as Potential Novel Efflux Pump Inhibitors of the TolC Channel in E. Coli Strains

Date of Award

1-1-2018

Degree Name

M.S. in Chemistry

Department

Department of Chemistry

Advisor/Chair

Advisor: Matthew Lopper

Abstract

Microbial antibiotic resistance is a contemporary challenge threatening the health system worldwide. According to World Health Organization, previous cases of bacterial infections - once treatable with antibiotics - can now be lethal due to the uncontrolled misuse of these agents. One of the main triggers of bacterial resistance is the over-expression of multi-drug resistant (MDR) efflux pumps. These pumps allow the bacterium to pump antibiotics out of the cell and therefore desensitizes the cells to the antibacterial inhibitory effect. In this thesis, I evaluated the efflux pump inhibitory activity of eight different plant extracts using the Gram negative bacterium, E. coli. I also described the development of synthetic nucleic acids called aptamers to bind to and block the outer membrane channel of the efflux pump TolC as another effective way to impede antibiotic resistant bacteria from effluxing antibiotics. To generate the DNA aptamers exhibiting a binding specificity to E. coli cells, the method of a whole-cell Systemic evolution of Ligands by Exponential enrichement (SELEX) was applied to a random single-stranded DNA library. The efflux pump inhibiting activity of the plant extracts and the DNA aptamers was evaluated using an in-vivo efflux assay.

Keywords

Chemistry, Biochemistry, antibiotic resistance, aptamers, efflux pumps, E coli, plant extracts

Rights Statement

Copyright 2018, author

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