The Persister Problem
: Developing Assays to target persister cells in antibiotic screening studies

  • Matthew C. Smith

Student thesis: Master's ThesisMaster of Science

Abstract

Persister cells are non-growing cells, which are thought to have low levels of metabolic activity. These cells are often more tolerant against antibiotic treatments due to conventional antibiotics typically targeting cell division, growth and metabolism often leading to relapse in patients suffering from acute and chronic infections. Because of this there is a need to develop drugs which can specifically target these persister cells and improve the efficacy of existing antibiotics. In this project we aimed to develop and implement a novel assay in which we could specifically screen drugs on their ability to completely clear these antibiotic tolerant infections and to screen known unique compounds with this assay.

We also investigated the hits we generated from this assay by developing and utilising GFP reporter strains to establish potential mechanism of action of the hits to investigate the potential link between efflux and persister cells.
Date of Award2022
Original languageEnglish
SupervisorMegan Bergkessel (Supervisor) & Kevin Read (Supervisor)

Keywords

  • Persister Cells
  • Drug Screening
  • Antibiotic tolerance
  • drug discovery
  • Assay development
  • GFP reporter strains
  • Pseudomonas Aeruginosa

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