Abstract
This thesis explores the intricate interactions between Pseudomonas aeruginosaand Staphylococcus aureus within polymicrobial biofilms and their impact on
antimicrobial susceptibility. By focusing on mixed-species biofilms, this research
aims to better understand how these bacteria influence each other’s growth and
response to different treatments.
Strain-specific interactions were studied using eight P. aeruginosa strains and seven S. aureus strains in both planktonic and biofilm states in two distinct growth media. Cooperative, competitive, and exploitative interactions were observed, with variations depending on the specific strain combinations and environmental conditions. To uncover the mechanisms underpinning these interactions, metabolomic analyses were performed using nuclear magnetic resonance (NMR) spectroscopy on three selected P. aeruginosa–S. aureus strain pairs. These pairs were chosen based on the diversity of their biofilm interactions. Key metabolites including adenosine, ethanol, formate, 6-hydroxynicotinic acid, ethylene glycol, mannose and propylene glycol involved in interspecies interactions were identified, shedding light on potential metabolic pathways that contribute to biofilm dynamics.
The efficacy of traditional antibiotics was shown to vary greatly in these mixed-species biofilms compared to single-species biofilms, and the potential of non-traditional therapies in combating biofilm-associated infections was also explored. This thesis demonstrates that alternative treatments show promise in overcoming the resistance observed in polymicrobial biofilms. A novel approach to the controlled release of phages from hydrogels was also tested, demonstrating promising results in reducing bacterial viability. An investigation into the reasons behind the development of tolerance to ciprofloxacin in P. aeruginosa NCTC10662 within a mixed biofilm with S. aureus USA300 provided insights into complex interplay between these species in polymicrobial environments.
This research provides valuable insights into the complexity of biofilm-associated
infections and the challenges posed by microbial interactions in clinical settings. It emphasizes the need for targeted, combination therapies that account for the
dynamic interplay between microbial species to effectively manage biofilm-related infections and improve treatment outcomes and highlights the importance of using clinically relevant biofilm models to test novel therapeutics.
| Date of Award | 8 Oct 2025 |
|---|---|
| Original language | English |
| Awarding Institution |
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| Supervisor | Petra Cameron (Supervisor), Maisem Laabei (Supervisor) & Toby Jenkins (Supervisor) |
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