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dc.contributor.authorNorville, Isobel Harrieten_GB
dc.date.accessioned2011-06-22T13:42:13Zen_GB
dc.date.accessioned2013-03-21T10:31:37Z
dc.date.issued2011-03-04en_GB
dc.description.abstractThe aim of this study was to identify and characterise peptidyl-prolyl cis-trans isomerases (PPIases) from the bacterium Burkholderia pseudomallei, the causative agent of the disease melioidosis. The longer term goal was to assess their potential as vaccine candidates or antimicrobial targets. Using bioinformatic approaches, six putative FK506-binding proteins (FKBPs) proteins and three putative parvulin proteins were identified in B. pseudomallei. Of these, six were expressed and purified as recombinant proteins. The purified proteins were used to immunise BALB/c mice, with some providing protection against a subsequent B. pseudomallei infection. These proteins could therefore be proposed as potential vaccine candidates. Homologues of Mip or SurA, which are associated with virulence in other bacterial species, were identified in B. pseudomallei and closely related B. thailandensis. Recombinant Mip or SurA homologues from B. pseudomallei were shown to have characteristic PPIase enzyme activity. To evaluate the role of the Mip homologue from B. pseudomallei in virulence, an unmarked deletion mutant was constructed. The mutant had reduced intracellular survival; defects in putative virulence mechanisms and attenuated virulence in mice. To assess the role of a SurA homologue, closely related B. thailandensis was used as a model organism, with deletion of the gene resulting in defects in intracellular infection, outer membrane integrity and virulence. This indicates that PPIases from B. pseudomallei and B. thailandensis represent novel virulence determinants and potential antimicrobial targets for therapeutics against melioidosis.en_GB
dc.description.sponsorshipMinistry of Defenceen_GB
dc.identifier.urihttp://hdl.handle.net/10036/3152en_GB
dc.language.isoenen_GB
dc.publisherUniversity of Exeteren_GB
dc.rights© Crown copyright 2011. Published with the permission of the Defence Science and Technology Laboratory on behalf of the Controller of the HMSO.en_GB
dc.subjectBurkholderia pseudomalleien_GB
dc.subjectPPIaseen_GB
dc.subjectMipen_GB
dc.subjectSurAen_GB
dc.titleThe identification and characterisation of PPIases from Burkholderia pseudomallei and Burkholderia thailandensisen_GB
dc.typeThesis or dissertationen_GB
dc.date.available2011-06-22T13:42:13Zen_GB
dc.date.available2013-03-21T10:31:37Z
dc.contributor.advisorTitball, Richarden_GB
dc.contributor.advisorSarkar-Tyson, Mitalien_GB
dc.publisher.departmentCollege of Life and Environmental Sciencesen_GB
dc.type.degreetitlePhD in Biological Sciencesen_GB
dc.type.qualificationlevelDoctoralen_GB
dc.type.qualificationnamePhDen_GB


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