ORCID ID
Graduation Date
12-15-2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Programs
Immunology, Pathology & Infectious Disease
First Advisor
Prabagaran Narayanasamy
Abstract
Antimicrobial resistance is an incredibly pressing issue in modern medicine. Because of that many researchers are pursuing just as many avenues for treatment of these pathogens. However, due to the nature of bacteria many of these methods are stop gaps and the bacteria can develop typically within years of their deployment. Therefore, more robust methods of treating infections of antimicrobial resistant bacteria that are difficult or impossible to develop resistance to are required. To produce this effect the treatment would need to target and alter or inhibit functions or structures essential to the bacteria that could not be altered, additionally the treatment would need to be unaffected by enzymatic action like that done by carbapenemases. Our group believes that gallium-based therapeutics meet these criteria. In this research we investigated the effect of gallium nitrate and gallium protoporphyrin on the antimicrobial resistant bacteria Pseudomonas aeruginosa, and Klebsiella pneumoniae. We determined their effects on bacterial killing alone and in combination. We evaluated potential mechanisms of action and investigated the potency of the combination treatment in a murine lung infection model. Our research provides evidence that gallium compounds particularly the combination therapy of gallium nitrate and gallium protoporphyrin are an effective means of treating antimicrobial resistant bacteria and that the treatment may function through the inhibition of ROS defense mechanisms.
Recommended Citation
Scott, Zachary, "Investigating and Targeting Iron Metabolism in Pseudomonas Aeruginosa and Klebsiella Pneumoniae" (2023). Theses & Dissertations. 777.
https://digitalcommons.unmc.edu/etd/777
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Comments
2023 Copyright, the authors