An Investigation of Bacterial Efflux Pump Inhibitors

Date of Award

2022

Degree Name

M.S. in Chemistry

Department

Department of Chemistry

Advisor/Chair

Matthew Lopper

Abstract

Multidrug resistance in bacteria, defined as the ability of a bacterial strain to resist the killing effects of more than one antibiotic, represents a major threat to global healthcare. Every year in the United States, two million people are infected with a multidrug resistant strain of bacteria. According to the Center for Disease Control (CDC), out of those two million people, about 35,000 will die from their infection. Thus, these multidrug resistant diseases are considered by the CDC to be the most dangerous diseases in the world. While multidrug resistance can occur through several different mechanisms, a major contributor to multidrug resistance are the bacterial efflux pumps. Efflux pumps are transporters that reside in the membrane of a bacterial cell, and they function by pumping out toxic organic compounds, including antibiotics, from the cell. These efflux pumps often lack specificity for the compounds that they can expel from the cell which means that a single type of efflux pump can confer resistance to many types of antibiotics all at once. When bacterial cells produce high levels of these efflux pumps in their membranes, it can give rise to a multidrug resistance characteristic. We investigated the use of single-stranded DNA aptamers that we developed using a Cell-SELEX procedure and synthesized 1-napthylmethylpiperazine (NMP) derivatives to test as potential efflux pump inhibitors. We determined inhibition activity using growth curve assays with and without levofloxacin. We were not able to generate any ssDNA aptamers that can block the efflux pump. However, we were able to synthesis a NMP derivative that had antimicrobial effects by comparing it to NMP.

Keywords

Biochemistry, Department of Chemistry

Rights Statement

Copyright © 2022, author.

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