Antimicrobials and Antimicrobial Resistance (AAMR)
The antibiotic resistance crisis is threatening the future of modern healthcare and the discovery of solutions will involve collaboration and investigation into multiple avenues of research. This work involved two projects, the first investigating plasmid transmission and the spread of antibiotic re...
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| Format: | Thesis (University of Nottingham only) |
| Language: | English |
| Published: |
2019
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| Online Access: | https://eprints.nottingham.ac.uk/59222/ |
| Summary: | The antibiotic resistance crisis is threatening the future of modern healthcare and the discovery of solutions will involve collaboration and investigation into multiple avenues of research. This work involved two projects, the first investigating plasmid transmission and the spread of antibiotic resistance genes (ARGs). The second focussed on developing tools to monitor Staphylococcus aureus biofilm growth.
ARGs can be spread between bacteria of the same or different species by horizontal gene transfer on plasmids. Transmission of plasmids can be specific to each host- plasmid interaction therefore it is important to monitor plasmid transmission in clinically relevant hosts. This project involved developing a fluorescence-based system used for monitoring the spread of ß-lactamase carrying plasmids. The system has been established for monitoring transmission of pCT and pKpQIL in single-species environments, the aim was to establish this with pNDM-HK, a globally disseminated AMR plasmid. The second focus was to develop the system with pCT and pKpQIL to enable monitoring of plasmid movement in multi-species environments. The assay can be used to screen for inhibitors of plasmid conjugation to prevent the spread of antibiotic resistance plasmids.
The second project involved developing tools for evaluation of S. aureus biofilm growth. Growth in biofilms protects bacteria from antibiotics and the host immune response making infections hard to clear. Phenotypic analysis of S. aureus biofilm growth was performed on ceramic beads as tooth models and cytodex beads which are used as supports in virulence models in vivo. Biofilms were visualised using confocal microscopy. Biofilms were grown in artificial saliva media to mimic biofilm growth in the mouth which is a reservoir for staphylococci that can disseminate around the body. A strain with a knockout of the agr system was analysed as this has a role in control of biofilm growth. Confocal microscopy was also used to determine the spatial heterogeneity of S. aureus biofilms to give insights for drug target development. |
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