Graduation Term

2023

Degree Name

Master of Science (MS)

Department

School of Biological Sciences

Committee Chair

Jan Dahl

Abstract

Due to the rise in antimicrobic resistance and the decline in antibiotic discovery, drug development has expanded into alternative antimicrobial compounds, such as silver. Silver-containing compounds have emerged as a promising alternative due to their multi-specific effects on inhibiting bacterial growth. Our work focuses on the antimicrobial effects of AGXX, a novel antimicrobial which has been shown to exert its broad-spectrum effects through the production of highly cytotoxic reactive oxygen species (ROS). Although preliminary studies have demonstrated the potency of AGXX in gram-positive pathogens, its effects on gram-negative pathogens remain largely unknown. The goal of my thesis was to examine the dynamics of AGXX’s activity alone and in combination with conventional antibiotics against a notoriously antibiotic-resistant opportunistic pathogen Pseudomonas aeruginosa. I found that combining AGXX with aminoglycosides at sub-lethal concentrations exponentially reduced bacterial survival. This synergistic relationship is contingent on the generation of ROS and increased uptake and accumulation of aminoglycoside antibiotics in P. aeruginosa. More importantly, the aminoglycoside synergizing effects of AGXX was applicable to drug resistant clinical isolates and even gram-positive pathogens.

Access Type

Thesis-Open Access

DOI

https://doi.org/10.30707/ETD2023.20231004061828081611.999984

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