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Download StatisticsWang Kan, Xuan (2019). The role of the AcrB multidrug resistance efflux pump in the biology of Salmonella enterica serovar Typhimurium. University of Birmingham. Ph.D.
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WangKan2019PhD.pdf
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Abstract
Efflux pumps confer multidrug resistance to bacteria by exporting drugs and preventing them from reaching their target. The most abundant and best studied efflux pump in Salmonella Typhimurium is AcrB. The biological function of AcrB was unexplored. Therefore, the impact of loss of AcrB-mediated efflux was studied in S. Typhimurium, using an AcrB D408A mutant, which expressed an inactive form of AcrB.
Transcriptomics studies revealed significant differences between the AcrB D408A mutant and previously constructed ΔacrB and acrB::aph mutants, which did not express AcrB. The acrB::aph mutant differed in the motility phenotype from the other two mutants. However, all three mutants were multidrug hypersusceptible and were attenuated when compared against their parental wild-type strain. AcrB-mediated efflux also had a role in quorum sensing, persister formation and maintenance of the overall metabolic state of Salmonella. Analysis of the effluxome of AcrB in S. Typhimurium and E. coli revealed that fatty acids/alcohols are a common substrate of AcrB in both species and acylcarnitines were exclusive to S. Typhimurium.
This study presents a novel model to analyse the physiological role of RND efflux pumps and demonstrates that AcrB is more than just a mechanism of antibiotic resistance.
| Type of Work: | Thesis (Doctorates > Ph.D.) | |||||||||
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| Award Type: | Doctorates > Ph.D. | |||||||||
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| Licence: | All rights reserved | |||||||||
| College/Faculty: | Colleges (2008 onwards) > College of Life & Environmental Sciences | |||||||||
| School or Department: | Institute of Microbiology and Infection | |||||||||
| Funders: | Other | |||||||||
| Other Funders: | Professor Sir Charles George, Arjang G. Zadeh, CONACyT | |||||||||
| Subjects: | Q Science > QR Microbiology | |||||||||
| URI: | http://etheses.bham.ac.uk/id/eprint/9188 |
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