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dc.contributor.advisorHansen, Eric J.en
dc.creatorMock, Jason Roberten
dc.date.accessioned2010-07-12T18:42:13Zen
dc.date.available2010-07-12T18:42:13Zen
dc.date.issued2007-05-22en
dc.identifier.other761319384en
dc.identifier.urihttp://hdl.handle.net/2152.5/641en
dc.description.abstractHaemophilus ducreyi, the etiologic agent of the sexually transmitted disease chancroid, has been shown to inhibit phagocytosis of both itself and secondary targets in vitro. This inhibitory activity was previously shown to be abrogated by inactivation of the lspA1 and lspA2 genes of this pathogen. Avoidance of phagocytosis has been suggested to be a primary method by which H. ducreyi persists in humans, and subsequently allows the ulcerative disease process to occur. Like other genital ulcerative diseases, chancroid is associated with an increased risk for acquisition and transmission of the human immunodeficiency virus (HIV), and is an important cofactor in HIV spread in areas where chancroid is prevalent. My studies have focused on the regulation and mechanism of action of the LspA proteins. The regulation studies have demonstrated that transcriptional regulation of these large extracellular virulence factors does occur, and also suggest that other outer membrane proteins may be regulated by a similar method. Work elucidating the mechanism of action of the LspA proteins has identified a decrease in catalytic activity of Src family protein tyrosine kinases in macrophages exposed to wild-type H. ducreyi, leading to a halt in phagocytic cup formation and a subsequent decrease in uptake of opsonized targets. Additional experiments suggest a possible membrane component in immune cells may be responsible for relaying the LspA proteins' inhibitory signal. This is the first example of a bacterial pathogen that suppresses Src family protein tyrosine kinase activity to subvert phagocytic signaling in host cells.en
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.language.isoenen
dc.subjectHaemophilus ducreyien
dc.subjectPhagocytosisen
dc.subjectsrc-Family Kinasesen
dc.titleThe LspA Proteins Of Haemophilus Ducreyi: Extracellular Virulence Factorsen
dc.type.materialTexten
dc.type.genredissertationen
dc.format.digitalOriginborn digitalen
thesis.degree.grantorGraduate School of Biomedical Sciencesen
thesis.degree.departmenten
thesis.degree.nameDoctor of Philosophyen
thesis.degree.levelPh.D.en
thesis.degree.disciplineMolecular Microbiologyen
thesis.date.available2009-05-22en


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