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Investigations into the roles of bacteroides fragilis thioredoxins during the oxidative stress response

dc.contributor.advisorSmith, Charles Jeffreyen_US
dc.contributor.authorReott, Michael A., Jr.en_US
dc.contributor.departmentMicrobiology and Immunologyen_US
dc.date.accessioned2011-06-24T15:35:03Z
dc.date.available2013-07-01T11:15:48Z
dc.date.issued2011en_US
dc.description.abstractThe Gram-negative Bacteroides fragilis is the most frequently isolated bacterium from anaerobic infections. Native to the human intestinal tract, it serves a symbiotic role breaking down complex polysaccharides and restricting the growth of potentially harmful organisms. However, if translocated into the peritoneal cavity, B. fragilis can induce abscess formation; a potentially life-threatening condition. Although an obligate anaerobe, this bacterium is capable of surviving aerobic environments for extended periods of time, and its role as an opportunistic pathogen depends on this capability. Aerobic survival relies on an oxidative stress response of genes activated either dependently or independently by the stress response regulator OxyR. An important subset of OxyR-independent genes are the thioredoxins (Trxs). B. fragilis contains an extensive catalog of six trx genes, and analyses indicated each is differentially regulated during oxidative conditions. Single and multiple trx deletions were produced to determine functional differences of the proteins. It was found that trxA was essential for growth while no other single trx deletion conferred anaerobic growth defects. The trxD gene was found to be induced by the thiol oxidant diamide and TrxD was shown to be protective during exposure to diamide as well. In a trxD mutant strain, diamide-induced expression of trxC, trxE, and trxF increased significantly, suggesting compensatory effects in the Trx system. TrxD and TrxE were determined to be the only two B. fragilis Trxs capable of reducing the aerobic ribonucleotide reductase (NrdAB) of E. col , suggesting specificity of Trx targets in B. fragilis. Further investigations into TrxD determined the trxD promoter region and transcriptional start site as well as demonstrating TrxD to be the Trx primarily responsible for the reduction of specific oxidative stress-induced proteins including AsnB (asparaginase II) and Tps (thiol peroxidase scavengase). These data provide initial insight into both the specific and overlapping functions of Trxs in B. fragilis.  en_US
dc.description.degreePh.D.en_US
dc.format.extent138 p.en_US
dc.format.mediumdissertations, academicen_US
dc.identifier.urihttp://hdl.handle.net/10342/3595
dc.language.isoen_US
dc.publisherEast Carolina Universityen_US
dc.subjectMicrobiologyen_US
dc.subjectBiology, Molecularen_US
dc.subjectGeneticsen_US
dc.subjectAbscessesen_US
dc.subjectAnaerobeen_US
dc.subjectOxidative stressen_US
dc.subjectThiolen_US
dc.subjectE. coli
dc.subjectBiology, Genetics
dc.subjectBiology, Microbiology
dc.subjectMolecular biology
dc.subject.meshBacteroides
dc.subject.meshThioredoxins
dc.subject.meshInfection
dc.subject.meshPolysaccharides
dc.subject.meshPeritoneal Cavity
dc.subject.meshRibonucleotide Reductases
dc.subject.meshEscherichia coli
dc.subject.meshBacteroides fragilis
dc.titleInvestigations into the roles of bacteroides fragilis thioredoxins during the oxidative stress responseen_US
dc.typeDoctoral Dissertationen_US

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