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.
|Qualification||Doctor of Philosophy|
|Award date||9 Mar 2021|
|Publication status||Unpublished - 2021|