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dc.contributor.authorAndreae, Clio A.
dc.date.accessioned2014-07-30T07:55:59Z
dc.date.issued2014-05-02
dc.description.abstractBurkholderia pseudomallei is the causative agent of melioidosis, a disease endemic in Northern Australia and Southeast Asia. Melioidosis can present with acute, chronic and latent infections and can relapse several months or years after initial presentation. Currently not much is known about the ways in which B. pseudomallei can persist within the host, although it has been speculated that the ability to survive within an anaerobic environment will play some role. B. pseudomallei is able to survive anaerobically for extended periods of time but little is known about the molecular basis of anaerobic respiration in this pathogenic species. Bioinformatic analysis was used to determine the respiratory flexibility of both B. pseudomallei and B. thailandensis, identifying multiple genes required for aerobic and anaerobic respiration, and molybdopterin biosynthesis. Using B. thailandensis as a model organism a transposon mutant library was created in order to identify genes required for anaerobic respiration. From this library one transposon mutant was identified to have disrupted moeA, a gene required for the molybdopterin biosynthetic pathway. This B. thailandensis transposon mutant (CA01) was unable to respire anaerobically on nitrate, exhibiting a significant reduction in nitrate reductase activity, altered motility and biofilm formation, but did not affect virulence in Galleria mellonella. It was hypothesised that the reduction in nitrate reductase activity was contributing to the phenotypes exhibited by the B. thailandensis moeA transposon mutant. To determine whether this was true an in-frame narG deletion mutant was created in B. pseudomallei. Deletion of B. pseudomallei narG (ΔnarG) resulted in a significant reduction in nitrate reductase activity, anaerobic growth, motility and altered persister cell formation, and but did not affect virulence in G. mellonella or intracellular survival within J774A.1 murine macrophages. This study has highlighted the importance of anaerobic respiration in the survival of B. thailandensis and B. pseudomallei.en_GB
dc.description.sponsorshipBBSRCen_GB
dc.identifier.citationAndreae et al. 2014en_GB
dc.identifier.citationWagley et al. 2014en_GB
dc.identifier.urihttp://hdl.handle.net/10871/15284
dc.language.isoenen_GB
dc.publisherUniversity of Exeteren_GB
dc.subjectAnaerobic respirationen_GB
dc.subjectBurkholderia pseudomalleien_GB
dc.subjectBurkholderia thailandensisen_GB
dc.subjectNitrate reductaseen_GB
dc.subjectMolybdopterin Biosynthesisen_GB
dc.titleUnderstanding the Role of Anaerobic Respiration in Burkholderia Thailandensis and B. pseudomallei Survival and Virulenceen_GB
dc.typeThesis or dissertationen_GB
dc.date.available2014-07-30T07:55:59Z
dc.contributor.advisorButler, Clive S.
dc.contributor.advisorTitball, Richard W.
dc.publisher.departmentSchool of Bioscienceen_GB
dc.type.degreetitlePhD in Biological Sciencesen_GB
dc.type.qualificationlevelDoctoralen_GB
dc.type.qualificationnamePhDen_GB


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