Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.590484
Title: Model systems to investigate bacterial persistence to antibacterial agents
Author: Griffiths, Jennifer Mary
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2012
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Abstract:
Bacterial persistence describes the phenotypic variation displayed by clonal bacterial populations which permits a small fraction of cells to survive exposure to antimicrobials. The phenomenon was first described in the 19405 by Joseph Bigger who observed that penicillin could not sterilize a culture of Staphylococcus aureus. The surviving cells were not resistant mutants as they displayed equal susceptibility to penicillin as the parent population upon subculture. Among the various hypotheses which have been proposed to explain this phenomenon, the majority consider persisters to be dormant The prevailing model in Escherichia coli is that this behaviour results from stochastic expression of the toxic portion of chromosomal toxin-antitoxin modules. However, the exact mechanisms underlying this behaviour remain elusive, partly owing to the apparent redundancy of this phenotype. Persistence has been observed in all bacterial species tested to date however, most studies have focused on E. coli. This study aimed to explore the mechanisms of persistence in S. aureus by characterising two transposon insertion mutants identified as being defective in persistence to antimicrobials. The mutants were affected in different ABC transporter-like proteins, AbcA and PapA. The role of ABC transporters in persistence was further evaluated by independently inactivating abcA and papA. The resulting strains exhibited a reduced-persister phenotype to antimicrobials from different classes supporting a role for AbcA and PapA in S. aureus perSistence. The second part of this study sought to investigate the use of mycoplasmae as model systems for investigating persistence. Time-kill studies established that Mycoplasma hominis and Mycoplasma galliseptcium do generate persister cells. As neither organism has toxin-antitoxin modules in their genomes, the results imply that other mechanisms for persistence must exist. These mechanisms were investigated by generating and screening a M, gallisepticum transposon insertion library for genes involved in persistence. Four mutants with reduced persistence, disrupted in spoT, vlhA 1.04, asnA and MGA_0126, were identified.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.590484  DOI: Not available
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