Whole proteome approach to delineate leptospiral pathogenesis

Simple item page
dc.contributor.authorEshghi, Azad
dc.contributor.supervisorCameron, Caroline E.
dc.date.accessioned2011-12-16T18:40:45Z
dc.date.available2012-12-16T12:22:13Z
dc.date.copyright2011en_US
dc.date.issued2011-12-16
dc.degree.departmentDepartment of Biochemistry and Microbiology
dc.degree.levelDoctor of Philosophy Ph.D.en_US
dc.description.abstractThe study of leptospiral pathogenesis is hampered by the lack of efficient mutagenesis methodologies. Thus research has focused on alternative approaches including genome sequencing, comparative genomics, transcriptomics and proteomics. In this thesis a comparative proteomic approach was used to identify leptospiral proteins with a potential role in the leptospiral infection process. Identification of proteins was followed by characterization of target proteins with potential roles in the infection process and ultimately led to the identification of a novel leptospiral virulence factor. Specifically, comparative proteomics using isobaric tags for relative and absolute quantitation complemented with two-dimensional gel electrophoresis were used for mass spectrometry-based protein identification and quantitation. These methodologies were utilised to identify and quantitate leptospiral proteins altered in expression in response to growth media limited in iron supply and/or supplemented with serum. These conditions were designed to mimic a subset of variables encountered by the bacteria within the host. These experiments led to the identification of five proteins with potentially novel roles in the leptospiral infection process. One of these proteins was further characterized as a periplasmic catalase, KatE. Using insertion mutagenesis it was demonstrated that KatE enhances extracellular H2O2 resistance and is required for virulence in guinea pigs and hamsters. Proteomic analyses also led to the identification of glutamic acid methylation of a protein that was further characterised to be surface exposed and expressed during leptospiral colonization of hamster liver and kidneys. This was the first description of glutamic acid methylation of a surface exposed protein in Leptospira.en_US
dc.description.scholarlevelGraduateen_US
dc.identifier.bibliographicCitationGlobal Proteome Analysis of Leptospira interrogans Azad Eshghi, Paul A. Cullen, Laura Cowen, Richard L. Zuerner, Caroline E. Cameron Journal of Proteome Research 2009 8 (10), 4564-4578.en_US
dc.identifier.bibliographicCitationMethylation and in vivo expression of the surface-exposed Leptospira interrogans outer membrane protein OmpL32. Azad Eshghi, Marija Pinne, David A. Haake, Richard L. Zuerner, Ami Frank and Caroline E. Cameronen_US
dc.identifier.urihttp://hdl.handle.net/1828/3732
dc.language.isoenen_US
dc.rights.tempAvailable to the World Wide Weben_US
dc.subjectleptospiraen_US
dc.subjectspirocheteen_US
dc.subjectpathogenesisen_US
dc.subjectvirulenceen_US
dc.subjectmass spectroscopyen_US
dc.subjectMS/MSen_US
dc.subjectiTRAQen_US
dc.subject2DGEen_US
dc.titleWhole proteome approach to delineate leptospiral pathogenesisen_US
dc.typeThesisen_US

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Eshghi_Azad_PhD_2011.pdf
Size:
3.7 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.74 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

Electronic Theses and Dissertations (ETD)
 
University of Victoria Libraries

We acknowledge and respect the Lək̓ʷəŋən (Songhees and Esquimalt) Peoples on whose territory the university stands, and the Lək̓ʷəŋən and W̱SÁNEĆ Peoples whose historical relationships with the land continue to this day.