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A surface protease of Lyme disease bacteria degrades host extracellular matrix components and induces inflammatory cytokines in vitro

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dc.contributor.authorRussell, Theresa Michelle Tidd, author
dc.contributor.authorBamburg, James R., advisor
dc.contributor.authorJohnson, Barbara J. B., advisor
dc.contributor.authorLuger, Karolin, committee member
dc.contributor.authorCohen, Robert E., committee member
dc.contributor.authorGentry-Weeks, Claudia, committee member
dc.date.accessioned2007-01-03T05:58:41Z
dc.date.available2007-01-03T05:58:41Z
dc.date.issued2012
dc.description.abstractFor nearly two decades, the paradigm in Lyme disease research has been that Borrelia burgdorferi does not produce proteases capable of damaging host molecules. Lyme disease has been considered, therefore, to be the consequence of an exuberant inflammatory response to infecting bacteria. This prevailing concept, however, has created a conundrum for the field. The bacterial burden in infected tissue is low, but the degree of inflammation is remarkable and seemingly out of proportion to this burden. The studies described in this dissertation provide evidence that, contrary to current thinking, B. burgdorferi does possess a protease that degrades numerous molecules of the host extracellular matrix (ECM). In addition to destabilization of the ECM which would be expected to benefit the organism, characterization of this proteolytic activity demonstrates that ECM fragments are produced that are known to be pro-inflammatory. These bioactive fragments may amplify the inflammatory processes triggered by the presence of the bacteria itself. When this hypothesis was tested directly by exposing chondrocytes to the borrelial protease in vitro, inflammatory cytokines and chemokines that are hallmarks of Lyme disease were induced. The studies herein suggest a new model for the pathogenesis of Lyme disease and offer an explanation for the paradox of debilitating inflammatory disease in the presence of few infecting organisms. Lastly, in contrast to current serology-based Lyme disease diagnostic tests, the activity of this protease in vitro may generate diagnostic biomarkers enabling detection of active B. burgdorferi infection.
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierRussell_colostate_0053A_11447.pdf
dc.identifierETDF2012500359BAMB
dc.identifier.urihttp://hdl.handle.net/10217/80351
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.subjectBB0104
dc.subjectBbHtrA
dc.subjectcytokine/chemokine
dc.subjectLyme
dc.subjectprotease
dc.subjectproteoglycan
dc.titleA surface protease of Lyme disease bacteria degrades host extracellular matrix components and induces inflammatory cytokines in vitro
dc.typeText
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineBiochemistry and Molecular Biology
thesis.degree.grantorColorado State University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

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