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dc.contributor.authorMaunders, Eve Alexandra
dc.date.accessioned2018-10-02T14:45:49Z
dc.date.available2018-10-02T14:45:49Z
dc.date.issued2018-10-02
dc.date.submitted2018-06-06
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/283002
dc.description.abstractPseudomonas aeruginosa is an opportunistic human pathogen that is now the leading cause of morbidity and mortality in immunocompromised individuals. Those suffering with the genetic disease cystic fibrosis (CF) commonly encounter P. aeruginosa infections. P. aeruginosa infection can present itself as an acute infection, which is characterised by highly virulent, “free-swimming” bacteria, or as a chronic infection associated with the formation of surface-adhered bacterial communities known as biofilms. The labyrinth of interconnecting signalling networks has meant that the regulatory mechanisms behind biofilm formation and virulence are largely undefined. In this dissertation, a single nucleotide polymorphism was identified within the gene, fusA1, encoding elongation factor G (EF-G). The mutation introduced minor structural changes to the protein which were likely to have functional repercussions in its involvement in protein synthesis. Phenotypic analysis revealed that the mutation conferred changes in both resistance and sensitivity to various antibiotics, as well as changes in motility, exoenzyme production, quorum sensing, metabolism, synthesis of biofilm-associated proteins and exopolysaccharide production. Most notably was the up-regulation of a major virulence determinant, the type three secretion system, typically characteristic of cells comprising an acute infection. Proteomic and transcriptomic profiling of the mutant strain provided an insight into the genetic basis behind these phenotypes, identifying the up-regulation of multidrug efflux systems and modulations to the chemotactic systems. This study also found links between several biological processes that were modulated in the mutant strain, such as crosstalk between sulfur metabolism, iron uptake and the oxidative stress response. In summary, the work presented in this dissertation highlights the susceptibility of fusA1 to spontaneous mutation and identifies a novel role for EF-G in bacterial virulence and antibiotic sensitivity, both of which have worrying implications for infection within the CF lung.
dc.description.sponsorshipMedical Research Council King's College Cambridge Cambridge Philosophical Society
dc.language.isoen
dc.rightsAll rights reserved
dc.rightsAll Rights Reserveden
dc.rights.urihttps://www.rioxx.net/licenses/all-rights-reserved/en
dc.subjectBiofilm
dc.subjectPseudomonas
dc.subjectaeruginosa
dc.subjectvirulence
dc.subjecttype three secretion
dc.subjectfusA1
dc.subjectelongation factor G
dc.subjectEFG
dc.titleThe impact of a single nucleotide polymorphism in fusA1 on biofilm formation and virulence in Pseudomonas aeruginosa
dc.typeThesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnameDoctor of Philosophy (PhD)
dc.publisher.institutionUniversity of Cambridge
dc.publisher.departmentBiochemistry
dc.date.updated2018-09-05T17:17:20Z
dc.identifier.doi10.17863/CAM.30367
dc.publisher.collegeKing's college
dc.type.qualificationtitleBiochemistry
cam.supervisorWelch, Martin
cam.thesis.fundingtrue
rioxxterms.freetoread.startdate2019-10-02


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