Carlson, Paul Edward
(2008)
Recognition of Environmental Conditions Influences Francisella-Macrophage Interactions.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Francisella tularensis, the causative agent of tularemia, is a pathogen capable of survival and growth in a vast array of environments ranging from arthropod vectors to over one hundred different mammalian hosts, including humans. An understanding of the mechanisms that this bacterium uses to adapt to these varied environments is vital to fully understanding its pathogenesis. The environmental signals that Francisella responds to include low iron concentrations, oxidative stress, and temperature. The work described in this dissertation constitutes a significant step forward in our understanding of Francisella adaptation specifically to the host intracellular environment. We have shown that bacterial growth conditions have a great impact on bacterial phenotypes, particularly on the ability of Francisella to induce or inhibit macrophage cytokine production. We have identified a specific eukaryotic molecule, spermine, which is abundant in the intracellular environment and leads to significant changes in bacterial phenotypes and gene expression. We also present the first evidence of a role for the abundant Francisella IS elements in the regulation of transcription by functioning as spermine-responsive promoters. The ability of the bacterium to adapt to this signal is vital to its survival and a mutant lacking this sensing mechanism is highly attenuated. A thorough analysis of different culture conditions has lead to the identification of both known and putative virulence factors that may be important for altering host cell responses to F. tularensis. Our results demonstrate a novel mechanism of host-pathogen interaction and could have significant implications for other intracellular pathogens.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Carlson, Paul Edward | pec25@pitt.edu | PEC25 | |
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| ETD Committee: |
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| Date: |
24 April 2008 |
| Date Type: |
Completion |
| Defense Date: |
18 April 2008 |
| Approval Date: |
24 April 2008 |
| Submission Date: |
23 April 2008 |
| Access Restriction: |
5 year -- Restrict access to University of Pittsburgh for a period of 5 years. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
School of Medicine > Molecular Virology and Microbiology |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
Francisella; host-pathogen interaction; macrophage |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-04232008-140626/, etd-04232008-140626 |
| Date Deposited: |
10 Nov 2011 19:41 |
| Last Modified: |
15 Nov 2016 13:42 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/7565 |
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