Lethality of Staphylococcus in Murine Pneumonia is Due to Alpha-Toxin and Other Secreted Factors Regulated by AGR and SAR

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dc.contributor.advisorDan Dimitrijevich
dc.contributor.committeeMemberGlenn Dillon
dc.contributor.committeeMemberJames Caffrey
dc.creatorOverheim, Katie A.
dc.date.accessioned2019-08-22T21:09:59Z
dc.date.available2019-08-22T21:09:59Z
dc.date.issued2003-08-01
dc.date.submitted2013-11-05T06:54:04-08:00
dc.description.abstractOverheim, Katie A., Lethality of Staphlococcus aureus in Murine Pneumonia is Due to Alpha-Toxin and Other Secreted Factors Regulated by agr and sar. Doctor of Philosophy (Biomedical Sciences), August, 2003, 91 pp, 6 Tables, 9 illustrations, bibliography, 106. The purpose of these studies was to determine if the S. aureus global regulators agr and sar play a role in staphylococcal pneumonia and if the virulence factors regulated by them contributed to the severity of staphylococcal pneumonia. To determine this, we established a pneumonia model in mice in order to identify if S. aureus global regulators agr and sar play a role in the pathogenesis of staphylococcal pneumonia. As well, we took steps to identify the extracellular factors responsible for the lethality in a murine model of staphylococcal pneumonia and determine if these factors involved in disease process could be used as targets for immune therapy. My work revealed that lethal pneumonia in a mouse model is dependent on the S. aureus global regulators agr and sar. This study also revealed that the lethality associated with our model is due to secreted factors, regulated by S. aureus global regulators agr and sar. Further investigation demonstrated the alpha-toxin is a major virulence factor involved in the lethality in our model. By generating an alpha-toxin deficient strain in S. aureus RN6390, we show a reduced virulence in our disease model. As well, antiserum to alpha-toxin, when administered with a lethal dose of S. aureus RN6390, we show a reduced virulence in our disease model. As well, antiserum to alpha-toxin, when administered a lethal dose of S. aureus RN6390, we show a reduced virulence in our disease model. As well, antiserum to alpha-toxin, when administered with a lethal dose of S. aureus RN6390 protected animals from death. By evaluating the role of alpha-toxin’s ability to contribute to lethality, we assessed numerous strains of S. aureus in our pneumonia model. We discovered that there was a correlation to alpha-toxin production levels and lethality in our pneumonia model. However, our study also demonstrated that alpha-toxin is not the only factor involved in the disease process.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/29122
dc.language.isoen
dc.provenance.legacyDownloads0
dc.subjectBacteriology
dc.subjectComparative and Laboratory Animal Medicine
dc.subjectImmunology and Infectious Disease
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.subjectMicrobiology
dc.subjectOther Immunology and Infectious Disease
dc.subjectRespiratory System
dc.subjectRespiratory Tract Diseases
dc.subjectVirology
dc.subjectLethality
dc.subjectstaphylococcus aureus
dc.subjectmurine pneumonia
dc.subjectalpha-toxin
dc.subjectsecreted factors
dc.subjectagr
dc.subjectsar
dc.subjectdisease model
dc.titleLethality of Staphylococcus in Murine Pneumonia is Due to Alpha-Toxin and Other Secreted Factors Regulated by AGR and SAR
dc.typeDissertation
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.disciplineBiomedical Sciences
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

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