Date of Award
12-2021
Document Type
Thesis
Degree Name
Master of Science (MS)
Department
Biological Sciences
Committee Chair/Advisor
Dr. Tzuen-Rong Tzeng
Committee Member
Dr. Olin Thompson Mefford
Committee Member
Dr. Dan Simionescu
Abstract
With the increase of antibiotic resistant bacteria, current established therapeutic treatment methods are rapidly demonstrating decreasing efficacy. For this project, we are studying a novel alternate mechanism of treating antibiotic resistant bacteria by utilizing magnetic iron oxide nanoparticles (IONPs) coated with a heterobifunctional polyethylene glycol polymer (PEG) and functionalized with glycan structures that can interact with Neisseria gonorrhoeae FA1090. Interaction between the IONPs and bacteria is manipulated by an external alternating magnetic field (AMF) in a process known as magnetically mediated energy delivery (MagMED). Magnetic IONPs were synthesized and reacted with PEG (PEG-IONPs) and functionalized with glycans Gal(α1-3)Gal(β1-4)Glc(β1-1) (common name: Galili-tri), Gal(β1-4)Glc(β1-1) (common name: Lac) or (GalNAc(β1-4)Gal(β1-4)Glc-NAc-propargyl (common name: aGM2). Post synthesis and characterization, glycan functionalized IONPs were next used to treat N. gonorrhoeae FA1090 to determine the level of interaction between the IONPs and bacteria. N. gonorrhoeae was treated with Galili-tri -, Lac-IONPs, aGM2-IONPs and exposed to the MagMED system. Bacterial viability during MagMED exposure was monitored using viability PCR (vPCR) techniques. This vPCR method utilized the photoactivated dye propidium monoazide (PMA) and was refined for the detection of viable bacteria. Based on viability reduction, aGM2-IONPs were selected for investigation in an in vivo mouse model. A female Balb/c mouse model was utilized for the in vivo study and intravaginally inoculated with N. gonorrhoeae FA1090 to confirm the feasibility of using the model for an infection study. After confirmation of the N. gonorrhoeae infection, mice were treated using aGM2-IONPs, subjected to MagMED exposure and compared to a conventional antibiotic treatment method. The results indicated that aGM2-IONPs did not mediate significant reduction of the bacterial load under current treatment parameters when compared with the antibiotic treatment and further optimization is required for effective in vivo application. However, it was determined that the treatment of aGM2-IONPs and MagMED exposure had no adverse effects on the mice, supporting the previously determined biocompatibility of this method. This work demonstrates a novel alternative to conventional antibiotic treatments and serves to help the refinement of the technique in future research.
Recommended Citation
Taylor, Cedric, "Glycan Functionalization of Iron Oxide Nanoparticles (IONPs) As a Method of Inactivating Antibiotic Resistant Neisseria gonorrhoeae via a Magnetically Mediated Energy Delivery (MagMED) System" (2021). All Theses. 3668.
https://tigerprints.clemson.edu/all_theses/3668
Author ORCID Identifier
0000-0003-4949-5705