Year

2022

Degree Name

Doctor of Philosophy

Department

School of Civil, Mining, Environmental, and Architectural Engineering

Abstract

Antibiotic persistence occurs when a subpopulation of isogenic, antibiotic sensitive cells survives prolonged exposure to a bactericidal concentration of an antibiotic. This phenomenon has been shown to contribute to prolonged treatment duration, infection recurrence, as well as accelerated development of genetic resistance. Several molecular mechanisms have been demonstrated to influence formation of persister cells, however, the direct casual links between these mechanisms and persister cell formation remain to be established.

In this thesis we demonstrate that, contrary to previous reports, E. coli HipQ, a strain created during an untargeted mutagenesis screen known to produce a high number of antibiotic persisters, does not carry a mutation in the ydcI transcription factor. Subsequently, we present evidence suggesting that ydcI does not regulate persistence to β-lactams or fluoroquinolones. Furthermore, we show that the HipQ strain carries multiple other non-synonymous substitutions, in contrast to previously reported two single-nucleotide polymorphisms, including mutations in previously reported persistence regulators, which are likely to contribute to its high-persistence phenotype.

FoR codes (2008)

0605 MICROBIOLOGY

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Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.