dc.creator | Wiles, Karen Godfrey | |
dc.date.accessioned | 2020-08-22T20:58:24Z | |
dc.date.available | 2012-09-06 | |
dc.date.issued | 2010-09-06 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-09062010-113724 | |
dc.identifier.uri | http://hdl.handle.net/1803/14090 | |
dc.description.abstract | The work in this thesis involves characterization of a novel Streptococcus agalactiae-secreted protein, skizzle, and its interactions with key proteins of the human fibrinolytic system. Skizzle binds human plasminogen (Pg) with high affinity and acts as a cofactor of Pg activation to form the clot-dissolving protease, plasmin. As a cofactor, skizzle uses two different mechanisms to enhance Pg activation by the endogenous Pg activators, urokinase and tissue-type plasminogen activator. Skizzle-enhanced Pg activation by urokinase is specific for the circulating, unmodified form, [Glu]Pg, and involves a skizzle-induced Pg conformational change to a more-easily activated conformation. Enhanced activation of both unmodified [Glu]Pg and modified [Lys]Pg by tissue-type plasminogen activator involves formation of a skizzle-containing ternary or quaternary complex with Pg and tissue-type plasminogen activator, resulting in enhanced Pg activation. To our knowledge, skizzle is the first S. agalactiae-secreted cofactor of human Pg activation. Skizzle has the potential to be a virulence factor in the pathogenesis of life-threatening S. agalactiae infections of newborns and immune-compromised adults. | |
dc.format.mimetype | application/pdf | |
dc.subject | streptococcus agalactiae | |
dc.subject | skizzle | |
dc.subject | fibrinolysis | |
dc.subject | plasminogen | |
dc.title | Skizzle: a Novel Streptococcus agalactiae-secreted Cofactor of Human Plasminogen Activation | |
dc.type | dissertation | |
dc.contributor.committeeMember | Ingrid Verhammer | |
dc.contributor.committeeMember | David Gailani | |
dc.contributor.committeeMember | Andrzej Krezel | |
dc.contributor.committeeMember | Eric Skaar | |
dc.contributor.committeeMember | Paul E. Bock (advisor) | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Pathology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2012-09-06 | |
local.embargo.lift | 2012-09-06 | |
dc.contributor.committeeChair | Richard Hoover | |