Project 1: Elucidating the role of carbon storage regulator A, csrA, in regulating the AcrAB-TolC efflux system in Salmonella enterica serovar Typhimurium and Project 2: Exploring the dynamics of Pseudomonas aeruginosa attachment to host cells during anti-adhesion therapy

Attah, Victoria (2015). Project 1: Elucidating the role of carbon storage regulator A, csrA, in regulating the AcrAB-TolC efflux system in Salmonella enterica serovar Typhimurium and Project 2: Exploring the dynamics of Pseudomonas aeruginosa attachment to host cells during anti-adhesion therapy. University of Birmingham. M.Res.

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Abstract

Project 1: In MDR isolates of Enterobacteriaceae, except Escherichia coli and Shigella spp., RamA, locally regulated by RamR, activates the transcription of the tripartite efflux pump, AcrAB-TolC. TraDIS sequencing of Salmonella enterica serovar Typhimurium SL1344 generated gene-deletion mutants, which were interrogated with pMW82-pramA, encoding a green fluorescent protein (GFP) fused to the ramA promoter sequence. Disruption of the csrA gene in SL1344 resulted in a significant increase in the fluorescence of pMW82-pramA, therefore it was hypothesised that CsrA is involved in the regulation of RamA and the generation of antimicrobial resistance by upregulation of AcrAB-TolC. The aims of this study were to create and characterise a csrA::aph mutant in SL1344.
Project 2: There is an urgent need for alternative therapeutics to treat bacterial infections and limit the transmission of resistance. The attachment of bacteria to host cells is considered a prerequisite for bacteria to establish and propagate infection and anti-attachment therapies are well-documented; however, clinical treatments are currently unavailable. Mathematical modelling is a useful tool to model the efficacy of anti-virulence therapies in silico, particularly in combination with standard antibiotics, although, computer simulations based on theoretical values may limit the specificity of dosing regimens. The aims of this study were to generate experimental data in support of in silico modelling for anti-virulence therapy.

Type of Work: Thesis (Masters by Research > M.Res.)
Award Type: Masters by Research > M.Res.
Supervisor(s):
Supervisor(s)EmailORCID
Krachler, Anne-­MarieUNSPECIFIEDUNSPECIFIED
Piddock, LauraUNSPECIFIEDUNSPECIFIED
Licence:
College/Faculty: Colleges (2008 onwards) > College of Life & Environmental Sciences
School or Department: Institute of Microbiology and Infection
Funders: None/not applicable
Subjects: Q Science > QH Natural history > QH301 Biology
URI: http://etheses.bham.ac.uk/id/eprint/5566

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