Porter, Charlotte Emily (2025) Pseudomonas aeruginosa’s redox-active virulence factor pyocyanin and its genotoxic and cytotoxic impact on eukaryotic cells. Masters thesis, York St John University.
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Text (Masters by Research thesis)
Pseudomonas aeruginosa’s redox-active virulence factor pyocyanin and its genotoxic and cytotoxic impact on eukaryotic cells.pdf - Published Version Available under License Creative Commons Attribution. | Preview |
Abstract
Pseudomonas aeruginosa is an opportunistic pathogen, widely known for its chronic and severe infections in immunocompromised individuals, such as those with cystic fibrosis (CF). Pyocyanin, a virulence factor of P. aeruginosa, plays an important role in these infections. A redox-active phenazine pigment, pyocyanin promotes virulence via the formation of reactive oxygen species (ROS). ROS formation causes oxidative stress in cells, leading to DNA damage, compromised genomic stability, and increased risk of mutation accumulation and, subsequently, cancer. While pyocyanin’s redox abilities have been widely studied, its genotoxic effects on host cells remain unexplored. This study aims to explore the potential genotoxic and cytotoxic effects of pyocyanin on eukaryotic cells, focusing on human lymphocytes as a surrogate. Cell viability was assessed via the CCK-8 assay to determine the cytotoxic potential of pyocyanin. Single- and double-strand breaks were assessed via the Comet assay and PicoGreen assay to measure pyocyanin’s genotoxic effects. Pyocyanin was found to have a biphasic dose-response relationship with cell viability, with increased viability at low concentrations and cytotoxicity at high concentrations. Cell viability was enhanced over time up to concentrations of 10 µM pyocyanin. A dose-response increase in DNA damage was seen, with significant damage being reported across all concentrations. Evidence was also found to suggest that pyocyanin is an intercalating agent, producing falsely increased percentages of double-stranded DNA results in the PicoGreen assay. Overall, the findings highlighted a hormetic effect of pyocyanin which has not been previously established and its ability to induce DNA damage at low concentrations raises concerns about its impact on host cells, especially in those with chronic P. aeruginosa infections. Further research is necessary to investigate the genotoxic effects of long-term exposure to pyocyanin in addition to its hormetic effects, which may have therapeutic potential.
| Item Type: | Thesis (Masters) |
|---|---|
| Status: | Published |
| Subjects: | Q Science > Q Science (General) |
| School/Department: | School of Science, Technology and Health |
| URI: | https://ray.yorksj.ac.uk/id/eprint/12312 |
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