The role of host arginine metabolism in murine malaria
Abstract/Contents
- Abstract
- Infection disrupts host metabolism, but it is not well-known how the nature and magnitude of metabolic disruption relates to the severity of infectious disease. In this dissertation, I describe our efforts to uncover new links between metabolism and disease severity in murine malaria. To more closely model disease in a diverse population like that of humans, we infected eight genetically diverse, inbred mouse strains with Plasmodium chabaudi and tracked their symptomatic, pathological, immunological, and metabolic responses to acute infection. In chapter 2, we describe a wide range of disease severity and metabolic phenotypes in the eight strains. We use supervised and unsupervised techniques to identify metabolic biomarkers for severe disease that change in both murine and human Plasmodium infection. With this approach, we uncover arginine depletion as a specific indicator of P. chabaudi-induced liver damage. Given the established importance of arginine in malaria, chapters 3 and 4 describe how host enzymes that catabolize arginine affect infection severity. In chapter 3, we test the hypothesis that liver damage causes plasma arginine depletion by releasing hepatic arginase-1 into circulation and examine the role of host arginase-2 in limiting infection severity. In chapter 4, we characterize the role of nitric oxide synthases in P. chabaudi infection and find that host endothelial nitric oxide synthase promotes host tolerance to P. chabaudi infection. Collectively, this work leverages phenotypic diversity and genetic tools in inbred mice to improve our bioinformatic and mechanistic understanding of relationships between metabolism and infectious disease severity.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Davis, Nicole Marie |
|---|---|
| Degree supervisor | Schneider, David (David Samuel) |
| Thesis advisor | Schneider, David (David Samuel) |
| Thesis advisor | Jagannathan, Prasanna |
| Thesis advisor | Monack, Denise M |
| Thesis advisor | Sonnenburg, Justin, 1973- |
| Thesis advisor | Spormann, Alfred M |
| Degree committee member | Jagannathan, Prasanna |
| Degree committee member | Monack, Denise M |
| Degree committee member | Sonnenburg, Justin, 1973- |
| Degree committee member | Spormann, Alfred M |
| Associated with | Stanford University, Department of Microbiology and Immunology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Nicole Davis. |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology. |
| Thesis | Thesis Ph.D. Stanford University 2020. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Nicole Marie Davis
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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