Abstract
Staphylococcus aureus is increasingly resistant to antimicrobials. DNA plasmids carrying resistance genes generally cannot transfer autonomously but can be mobilised by self-transmissible conjugative plasmids if they carry a copy of the origin-of-transfer (oriT) sequence. In this thesis, oriT sequence recognition SmpO proteins were purified and analysed biochemically. SmpO proteins formed tetramers and specifically bound two sites within each oriT. DNA-binding site mutagenesis and surface-plasmon-resonance revealed SmpO proteins bound oriTs specifically but a single amino-acid change in SmpO switched oriT specificity in vitro and in vivo. These observations suggest conjugative plasmids can rapidly evolve to enable mobilisation of antimicrobial-resistance plasmids.
Original language | English |
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Qualification | Doctor of Philosophy |
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Award date | 9 Mar 2021 |
DOIs | |
Publication status | Unpublished - 2021 |