| dc.description.abstract | Rising precedence of antibiotic resistance has increased interest in nontraditional antibacterial agents such as zinc oxide nanoparticles (ZnO NPs). Although the anti-microbial activity of ZnO NPs is well established, the mechanism of this activity is unknown. Current literature hypothesizes that ZnO NP cytotoxicity could be mediated through one or multiple proposed mechanisms including production of reactive oxygen species (ROS), release of toxic ZnO2+ ions, and charged interactions that disrupt the cell wall and cause osmotic stress. Literature also suggests bacteria may be unable to gain resistance to ZnO because antibacterial action occurs through multiple mechanisms. To illuminate the properties of ZnO and determine which of the proposed mechanisms occur, ZnO susceptibility was assessed in Staphylococcus aureus. To determine if bacteria gain resistance to ZnO, S. aureus was passed in ZnO at sublethal doses. We find that S. aureus swiftly gain antibiotic resistance, suggesting ZnO antibacterial activity may operate through a single mechanism. To determine the predominant mechanism, susceptibility assays were performed in S. aureus mutants with deletions in katA, a gene important to defense against H2O2, and mprf, a gene important to cell wall charge. We find that production of H2O2 and charged interactions with the cell wall are not significant in ZnO susceptibility. Lastly, we find that media conditioned with ZnO effectively inhibits bacterial growth in the absence of ZnO particles. We conclude that physical contact with S. aureus is not necessary for ZnO activity, although the precise mechanism by which bacterial growth is inhibited is not yet elucidated. | |
