Molecular mechanisms of antibiotic-resistance gene transfer in Staphylococcus aureus

Karina Yui Eto

Research output: ThesisDoctoral Thesis

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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 languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • The University of Western Australia
Supervisors/Advisors
  • Bond, Charlie, Supervisor
  • Ramsay, Joshua, Supervisor
Thesis sponsors
Award date9 Mar 2021
DOIs
Publication statusUnpublished - 2021

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