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UBC Theses and Dissertations
Novel overlapping roles of Salmonella pathogenicity islands 1 and 2 in intestinal salmonellosis Coburn, Bryan
Abstract
Non-typhoidal Salmonella species are a significant cause of human diarrheal disease, incurring worldwide morbidity and mortality. The prevailing dogma arising from animal models of Salmonella enteropathogenesis is that the virulence associated genomic regions, Salmonella pathogenicity island (SPI) -1 and SPI-2, are essential for intracellular invasion/intestinal disease and intracellular survival/systemic disease, respectively. This paradigm partly reflects limitations of animal models currently used to study in vivo pathogenesis! In this thesis, a new model of murine Salmonella enteropathogenesis is presented which allows a novel examination of this theoretical dichotomy. Using this model, SPI-2 was shown to be required for complete enteropathogenesis in Salmonella enterica serovar Typhimurium infection. In addition, murine and bovine intestinal inflammation was identified in the absence of SPI-1, previously thought to be essential for intestinal disease. These findings are corroborated in human disease by the identification of a SPI-1 deficient human clinical diarrheal Salmonella enterica isolate. These strains were isolated from patients affected with severe diarrheal disease in Shenzhen, China. These are the first findings that demonstrate that SPI-2 is required for intestinal pathogenesis early in murine infection, and that SPI-1 is dispensible for enteropathogenesis in animal and human infections with S. enterica. These observations indicate that disease models, diagnostic and therapeutic approaches predicated on the requirement for SPI-1 in intestinal disease do not accurately describe intestinal salmonellosis.
Item Metadata
Title |
Novel overlapping roles of Salmonella pathogenicity islands 1 and 2 in intestinal salmonellosis
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
2006
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Description |
Non-typhoidal Salmonella species are a significant cause of human diarrheal disease, incurring
worldwide morbidity and mortality. The prevailing dogma arising from animal models of
Salmonella enteropathogenesis is that the virulence associated genomic regions, Salmonella
pathogenicity island (SPI) -1 and SPI-2, are essential for intracellular invasion/intestinal disease
and intracellular survival/systemic disease, respectively. This paradigm partly reflects
limitations of animal models currently used to study in vivo pathogenesis! In this thesis, a new
model of murine Salmonella enteropathogenesis is presented which allows a novel examination
of this theoretical dichotomy. Using this model, SPI-2 was shown to be required for complete
enteropathogenesis in Salmonella enterica serovar Typhimurium infection. In addition, murine
and bovine intestinal inflammation was identified in the absence of SPI-1, previously thought to
be essential for intestinal disease. These findings are corroborated in human disease by the
identification of a SPI-1 deficient human clinical diarrheal Salmonella enterica isolate. These
strains were isolated from patients affected with severe diarrheal disease in Shenzhen, China.
These are the first findings that demonstrate that SPI-2 is required for intestinal pathogenesis
early in murine infection, and that SPI-1 is dispensible for enteropathogenesis in animal and
human infections with S. enterica. These observations indicate that disease models, diagnostic
and therapeutic approaches predicated on the requirement for SPI-1 in intestinal disease do not
accurately describe intestinal salmonellosis.
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Genre | |
Type | |
Language |
eng
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Date Available |
2011-01-21
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0100343
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.