Discovery of Resistance-Reversing Agents in Antibiotic Resistant Strains of Escherichia coli and Klebsiella pneumoniae from Natural Product Libraries

Author

Andrew B. Watkins, University of Mississippi. Sally McDonnell Barksdale Honors College

Date of Award

2015

Document Type

Undergraduate Thesis

Department

Pharmaceutics and Drug Delivery

First Advisor

Alice Clark

Relational Format

Dissertation/Thesis

Abstract

Objective: The objective of this exploratory research is to discover compounds, particularly from natural products, that inhibit ESBL, KPC, and NDM-1 mechanisms of antibiotic resistance in the Gram negative bacteria Escherichia coli and Klebsiella pneumoniae. Methods: This objective will be accomplished utilizing a high-volume bioassay testing natural product samples from the National Center for Natural Products Research. This assay tests samples against 6 different strains of bacteria known to express β-lactamases in the presence and absence of sub-inhibitory concentrations of the test antibiotic. By structuring the assay in this way, differentiation may be made between the inherent antibacterial activity of samples and the synergistic effects between the sample and the antibiotic. Optical density (OD) readings will be used to determine bacterial growth or the lack thereof. Samples showing pronounced activity only in the presence of the antibiotics will be considered active and will be tested in a checkerboard assay to confirm activity. Results: Of over 5,000 samples tested, 35 samples showed synergistic activity, giving a hit rate of 0.7%. Of these 35, the most promising three hits were tested in follow-up checkerboard assays. These three samples all demonstrated synergistic effects with fractional inhibitory concentrations (FIC) of <0.5. Of the samples tested in the checkerboard assays, one was a plant extract, one was a pure compound, and one was a fungal soil isolate obtained from the National Cancer Institute. Conclusions: This study showed the benefits of using a high-volume screen to test samples against resistant bacterial strains. Continued research in this field could prove to be beneficial to the discovery of new drugs for clinically relevant therapeutic applications.

Recommended Citation

Watkins, Andrew B., "Discovery of Resistance-Reversing Agents in Antibiotic Resistant Strains of Escherichia coli and Klebsiella pneumoniae from Natural Product Libraries" (2015). Honors Theses. 1251.
https://egrove.olemiss.edu/hon_thesis/1251

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