An Investigation into the utilisation of ethanolamine by uropathogenic E. coli

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dc.check.embargoformatApply the embargo to the e-thesis on CORA (If you have submitted an e-thesis and want to embargo it on CORA)en
dc.check.entireThesisEntire Thesis Restricted
dc.check.opt-outNot applicableen
dc.check.reasonThis thesis contains data which has not yet been publisheden
dc.contributor.advisorMacSharry, Johnen
dc.contributor.advisorPrentice, Michael B.en
dc.contributor.authorDadswell, Katherine
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2019-05-08T10:59:05Z
dc.date.issued2019
dc.date.submitted2019
dc.description.abstractUrinary tract infections (UTIs) are one of the most common bacterial infections worldwide with E. coli as the causal organism responsible for 75% of all cases. Uropathogenic E. coli (UPEC) naturally reside in the gastrointestinal tract (GI tract) and infect the urinary tract via migratory ascension of the urethra. Ethanolamine, an amino alcohol found naturally in phospholipids as phosphatidylethanolamine, can be metabolised by bacteria to be used as an alternate source of nitrogen and carbon. Within the GI tract ethanolamine provides pathogenic bacteria with a competitive advantage over the commensal bacteria. The ability of bacteria to utilise ethanolamine is dependent on the presence of the ethanolamine utilisation (eut) operon encoding enzymes and bacterial microcompartment packaging. Recent studies suggest the regulator of the eut operon, eutR, can modulate the expression of virulence factors in Enterohaemorrhagic E. coli (EHEC). Transcriptome analysis of UPEC in active UTIs has found that the eut operon is expressed within the urinary tract and confers a competitive advantage in the murine urinary tract, but the exact mechanism conferring this advantage is not known. The aim of this thesis was to investigate the utilisation of ethanolamine by UPEC. This thesis provides evidence that ethanolamine is present in the urine at concentrations of approximately 0.57mM and correlated with the expression of the eut operon in UPEC infected urine. Additionally, the ability to metabolise ethanolamine by the eut operon is conserved across UPEC in this cohort (Cork University Hospital, Cork). Ethanolamine provides UPEC with a growth advantage as a sole nitrogen source in modified M9 minimal medium and an artificial urine medium (AUM). Metabolite analysis shows that the growth advantage observed in both media correlates with ethanolamine metabolism. Expression of eut operon genes and electron microscopy evidence of bacterial microcompartment formation was found in UPEC strain U1 metabolising ethanolamine in AUM. Mutational analysis confirmed a requirement for a functional eut operon to metabolise ethanolamine and suggests that ethanolamine is utilised by UPEC as an additional carbon source. Ethanolamine provide U1 with a competitive growth advantage at 10mM concentrations in vitro. RT-PCR provides evidence that suggests ii ethanolamine regulated the expression of type 1 fimbriae in U1. In conclusion, this thesis supports the hypothesis that ethanolamine provides UPEC with a growth advantage in urine with a potential role in the pathogenicity of UTIs.en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationDadswell, K. 2019. An Investigation into the utilisation of ethanolamine by uropathogenic E. coli. PhD Thesis, University College Cork.en
dc.identifier.endpage178en
dc.identifier.urihttps://hdl.handle.net/10468/7864
dc.language.isoenen
dc.publisherUniversity College Corken
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/en
dc.rights© 2019, Katherine Dadswell.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectUPECen
dc.subjectEthanolamineen
dc.subjectUTIen
dc.subjectMetabolismen
dc.subjectBacterial microcompartmentsen
dc.subjectEscherichia colien
dc.thesis.opt-outfalse
dc.titleAn Investigation into the utilisation of ethanolamine by uropathogenic E. colien
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhDen
ucc.workflow.supervisorm.prentice@ucc.ie
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