Helicobacter pylori: comparative genomics and structure-function analysis of the flagellum biogenesis protein HP0958

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dc.check.embargoformatBoth hard copy thesis and e-thesisen
dc.check.entireThesisEntire Thesis Restricted
dc.check.opt-outNot applicableen
dc.check.reasonThis thesis is due for publication or the author is actively seeking to publish this materialen
dc.contributor.advisorO'Toole, Paul W.en
dc.contributor.authorde Lacy Clancy, Ceara A.
dc.contributor.funderIrish Research Councilen
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2014-10-06T16:28:16Z
dc.date.available2015-10-07T04:00:05Z
dc.date.issued2014
dc.date.submitted2014
dc.description.abstractHelicobacter pylori is a gastric pathogen which infects ~50% of the global population and can lead to the development of gastritis, gastric and duodenal ulcers and carcinoma. Genome sequencing of H. pylori revealed high levels of genetic variability; this pathogen is known for its adaptability due to mechanisms including phase variation, recombination and horizontal gene transfer. Motility is essential for efficient colonisation by H. pylori. The flagellum is a complex nanomachine which has been studied in detail in E. coli and Salmonella. In H. pylori, key differences have been identified in the regulation of flagellum biogenesis, warranting further investigation. In this study, the genomes of two H. pylori strains (CCUG 17874 and P79) were sequenced and published as draft genome sequences. Comparative studies identified the potential role of restriction modification systems and the comB locus in transformation efficiency differences between these strains. Core genome analysis of 43 H. pylori strains including 17874 and P79 defined a more refined core genome for the species than previously published. Comparative analysis of the genome sequences of strains isolated from individuals suffering from H. pylori related diseases resulted in the identification of “disease-specific” genes. Structure-function analysis of the essential motility protein HP0958 was performed to elucidate its role during flagellum assembly in H. pylori. The previously reported HP0958-FliH interaction could not be substantiated in this study and appears to be a false positive. Site-directed mutagenesis confirmed that the coiled-coil domain of HP0958 is involved in the interaction with RpoN (74-284), while the Zn-finger domain is required for direct interaction with the full length flaA mRNA transcript. Complementation of a non-motile hp0958-null derivative strain of P79 with site-directed mutant alleles of hp0958 resulted in cells producing flagellar-type extrusions from non-polar positions. Thus, HP0958 may have a novel function in spatial localisation of flagella in H. pylorien
dc.description.sponsorshipIrish Research Council (EMBARK initiative); Science Foundation Ireland (Research Frontiers Programme award (09_RFP_GEN2443))en
dc.description.statusNot peer revieweden
dc.description.versionAccepted Version
dc.format.mimetypeapplication/pdfen
dc.identifier.citationde Lacy Clancy, C. A. 2014. Helicobacter pylori: comparative genomics and structure-function analysis of the flagellum biogenesis protein HP0958. PhD Thesis, University College Cork.en
dc.identifier.endpage290
dc.identifier.urihttps://hdl.handle.net/10468/1684
dc.language.isoenen
dc.publisherUniversity College Corken
dc.rights© 2014, Ceara A. De Lacy Clancy.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en
dc.subjectMicrobiologyen
dc.subjectHelicobacter pylorien
dc.subjectFlagellaen
dc.subjectGenomicsen
dc.thesis.opt-outfalse
dc.titleHelicobacter pylori: comparative genomics and structure-function analysis of the flagellum biogenesis protein HP0958en
dc.typeDoctoral thesisen
dc.type.qualificationlevelDoctoralen
dc.type.qualificationnamePhD (Science)en
ucc.workflow.supervisorpwotoole@ucc.ie
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