The LspA Proteins Of Haemophilus Ducreyi: Extracellular Virulence Factors

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The LspA Proteins Of Haemophilus Ducreyi: Extracellular Virulence Factors

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dc.contributor.advisor Hansen, Eric J. en
dc.creator Mock, Jason Robert en
dc.date.accessioned 2010-07-12T18:42:13Z en
dc.date.available 2010-07-12T18:42:13Z en
dc.date.issued 2007-05-22 en
dc.identifier.other 761319384 en
dc.identifier.uri http://hdl.handle.net/2152.5/641 en
dc.description.abstract Haemophilus 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.medium Electronic en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.subject Haemophilus ducreyi en
dc.subject Phagocytosis en
dc.subject src-Family Kinases en
dc.title The LspA Proteins Of Haemophilus Ducreyi: Extracellular Virulence Factors en
dc.type.material Text en
dc.type.genre dissertation en
dc.format.digitalOrigin born digital en
thesis.degree.grantor Graduate School of Biomedical Sciences en
thesis.degree.department en
thesis.degree.name Doctor of Philosophy en
thesis.degree.level Ph.D. en
thesis.degree.discipline Molecular Microbiology en
thesis.date.available 2009-05-22 en

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