Studies of Three Human Intestinal Opportunistic Pathogens

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dc.contributor.authorMastropaolo, Matthew Daviden
dc.contributor.committeecochairMelville, Stephen B.en
dc.contributor.committeecochairStevens, Ann M.en
dc.contributor.committeememberLarson, Timothy J.en
dc.contributor.committeememberInzana, Thomas J.en
dc.contributor.departmentBiologyen
dc.date.accessioned2014-03-14T20:14:46Zen
dc.date.adate2008-08-27en
dc.date.available2014-03-14T20:14:46Zen
dc.date.issued2008-07-30en
dc.date.rdate2009-08-27en
dc.date.sdate2008-08-05en
dc.description.abstractOpportunistic bacterial pathogens are present in the intestines of all mammals. These bacteria are symbionts to a certain extent, but under certain conditions these organisms can be deadly. Intestinal opportunistic pathogens encompass many genera and include organisms such as those in the Bacteroides fragilis group (i.e. B. fragilis and B. thetaiotaomicron), Escherichia coli, and Clostridium perfringens, resulting in an array of diseases and serious health risks. Typically these diseases affect individuals in poor or weakened health (elderly, immuno-compromised, neonates, etc.) but can affect healthy individuals as well. The intestinal tract is the main area of infection for these bacteria, however some of these organisms can be involved in wound infections, septicemia, urinary tract infections, and meningitis. This study focused on three areas: 1) Analysis of differences in gene expression between Bacteroides and Escherichia coli, in order to learn more about promoter structure, 2) Establishment of a diabetic mouse model for use in examining bacterial synergy during a polymicrobial infection, and 3) Characterization of Escherichia coli 360A and evaluation of the role of several virulence factors and environmental modulators in the pathogenesis of this strain. We used a newly developed lux gene reporter to evaluate gene expression in Bacteroides. We observed that there are barriers in both transcription and translation initiation that appear to limit the expression of foreign genes in Bacteroides. We were able to establish a mouse model for studying synergy during a polymicrobial infection and observed that E. coli 360A provided synergy towards B. fragilis NCTC 9343. These experiments also showed that the longer a mouse is afflicted with the complications of diabetes the more susceptible it is to polymicrobial infections. Systemic infections were used to evaluate the contribution of several virulence factors and environmental modulators in the pathogenesis of E. coli 360A. The results showed that a strain lacking both virulence factors CNF1 and HlyA, the terminal oxidase cytochrome o, or a double cyo/cyd mutant were, deficient in survival in the spleen, but not the liver of BALB/c mice.en
dc.description.degreePh. D.en
dc.identifier.otheretd-08052008-111424en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-08052008-111424/en
dc.identifier.urihttp://hdl.handle.net/10919/28529en
dc.publisherVirginia Techen
dc.relation.haspartMMastropaolodissertation.pdfen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectdiabetesen
dc.subjectmouse experimentsen
dc.subjectcytotoxic necrotizing factor 1en
dc.subjectα-hemolysinen
dc.subjectEscherichia colien
dc.subjectsystemic infectionen
dc.subjectcell cultureen
dc.subjectpolymicrobial infectionsen
dc.subjectlux reporteren
dc.subjectBacteroidesen
dc.titleStudies of Three Human Intestinal Opportunistic Pathogensen
dc.typeDissertationen
thesis.degree.disciplineBiologyen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePh. D.en

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