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dc.contributor.advisorJon D. Goguen
dc.contributor.authorPouliot, Kimberly Lea
dc.date2022-08-11T08:08:41.000
dc.date.accessioned2022-08-23T16:04:22Z
dc.date.available2022-08-23T16:04:22Z
dc.date.issued2007-12-20
dc.date.submitted2008-05-05
dc.identifier.doi10.13028/5ayn-7c77
dc.identifier.urihttp://hdl.handle.net/20.500.14038/31677
dc.description.abstractOf the eleven species of bacteria that comprise the genus Yersinia of the family Enterobacteriaceae, three species are pathogenic for humans. Yersinia pseudotuberculosis and Yersinia enterocolitica usually cause a mild, self-limiting mesenteric lymphadenitis or ileitis. Yersinia pestis causes a highly invasive often fatal disease known as plague. All three elaborate a type three secretion system that is essential for virulence and encoded on closely related plasmids. In Y. pestis, all the effectors, structural components and chaperones are encoded on the 70kb plasmid, pCD1. Of these, LcrV from Y. enterocolitica has been implicated in playing an immunosuppressive role through its interaction with host Toll-like receptor 2 (TLR2) and induction of IL-10. Through expression and purification of recombinant LcrV from Escherichia coliwe show that only high molecular weight species of rLcrV are able to stimulate TLR2. In a highly sensitive subcutaneous mouse infection model we demonstrate no difference in the time to death between TLR2-sufficient or deficient mice. Analysis of cytokine levels between these two genotypes also shows no significant difference between splenic IL-10 and IL-6 or levels of bacteria. We conclusively show that this interaction, if it does occur, plays no significant role in vivo. In a separate set of experiments, we also determined that the expression of F1, a peptide shown to be responsible for 37°C-dependent inhibition of invasion by Y. pestis in vitro, was significantly decreased under high oxygen conditions. This led us to re-examine the invasion phenotype both in vitro and in vivo. These results give new insights into virulence gene expression in Y. pestis by environmental cues other than temperature.
dc.language.isoen_US
dc.rightsCopyright is held by the author, with all rights reserved.
dc.subjectYersinia pestis
dc.subjectPlague
dc.subjectAntigens
dc.subjectBacterial
dc.subjectPore Forming Cytotoxic Proteins
dc.subjectToll-Like Receptor 2
dc.subjectSignal Transduction
dc.subjectVirulence Factors
dc.subjectOxygen
dc.subjectAmino Acids, Peptides, and Proteins
dc.subjectBacteria
dc.subjectBacterial Infections and Mycoses
dc.subjectBiological Factors
dc.subjectInorganic Chemicals
dc.titleSurface of Yersinia pestis: LCRV, F1 Production, Invasion and Oxygen: A Dissertation
dc.typeDoctoral Dissertation
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1358&context=gsbs_diss&unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_diss/358
dc.legacy.embargo2008-11-19T00:00:00-08:00
dc.identifier.contextkey504117
refterms.dateFOA2022-08-27T04:45:57Z
html.description.abstract<p>Of the eleven species of bacteria that comprise the genus <em>Yersinia</em> of the family <em>Enterobacteriaceae</em>, three species are pathogenic for humans. <em>Yersinia pseudotuberculosis</em> and <em>Yersinia enterocolitica</em> usually cause a mild, self-limiting mesenteric lymphadenitis or ileitis. <em>Yersinia pestis</em> causes a highly invasive often fatal disease known as plague. All three elaborate a type three secretion system that is essential for virulence and encoded on closely related plasmids. In <em>Y. pestis</em>, all the effectors, structural components and chaperones are encoded on the 70kb plasmid, pCD1.</p> <p>Of these, LcrV from <em>Y. enterocolitica</em> has been implicated in playing an immunosuppressive role through its interaction with host Toll-like receptor 2 (TLR2) and induction of IL-10. Through expression and purification of recombinant LcrV from <em>Escherichia coli</em>we show that only high molecular weight species of rLcrV are able to stimulate TLR2. In a highly sensitive subcutaneous mouse infection model we demonstrate no difference in the time to death between TLR2-sufficient or deficient mice. Analysis of cytokine levels between these two genotypes also shows no significant difference between splenic IL-10 and IL-6 or levels of bacteria. We conclusively show that this interaction, if it does occur, plays no significant role in vivo.</p> <p>In a separate set of experiments, we also determined that the expression of F1, a peptide shown to be responsible for 37°C-dependent inhibition of invasion by <em>Y. pestis in vitro</em>, was significantly decreased under high oxygen conditions. This led us to re-examine the invasion phenotype both <em>in vitro</em> and <em>in vivo</em>. These results give new insights into virulence gene expression in <em>Y. pestis</em> by environmental cues other than temperature.</p>
dc.identifier.submissionpathgsbs_diss/358
dc.contributor.departmentMicrobiology and Physiological Systems
dc.description.thesisprogramMolecular Genetics and Microbiology


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