Francisella tularensis host-pathogen relationships : dissecting bacterial interactions with the Drosophila innate immune system
Abstract/Contents
- Abstract
- The survival of a bacterial pathogen within a host depends upon its ability to outmaneuver the host immune response. Thus mutant pathogens provide a useful tool for dissecting host-pathogen relationships as the strategies the microbe has evolved to counteract immunity reveal a host's immune mechanisms. In this study, we examined the pathogen Francisella tularensis subspecies novicida and identified new bacterial virulence factors that interact with different parts of the Drosophila melanogaster innate immune system. We performed a genome-wide screen to identify F. novicida genes required for growth and survival within the fly and identified a set of 149 negatively selected mutants. Among these, we identified a class of genes including the transcription factor oxyR, and the DNA repair proteins uvrB, recB, and ruvC that help F novicida resist oxidative stress. We determined that these bacterial genes are virulence factors that allow F. novicida to counteract the fly melanization immune response. We then performed a second in vivo screen to identify an additional subset of bacterial genes that interact specifically with the imd signaling pathway. Most of these mutants have decreased resistance to the antimicrobial peptide polymyxin B. Characterization of a mutation in the putative transglutaminase FTN_0989 produced a curious result that could not easily be explained using known Drosophila immune responses. By using an unbiased genetic screen, these studies provide a new view of the Drosophila immune response from the perspective of a pathogen. We show that two branches of the fly's immunity are important for fighting F. novicida infections in a model host: melanization and an imd-regulated immune response, and identify bacterial genes that specifically counteract these host responses. Our work suggests that there may be more to learn about the fly immune system as not all of the phenotypes we observe can be readily explained by its interactions with known immune responses.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2010 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Moule, Madeleine Grace |
|---|---|
| Associated with | Stanford University, Department of Microbiology and Immunology |
| Primary advisor | Schneider, David (David Samuel) |
| Thesis advisor | Schneider, David (David Samuel) |
| Thesis advisor | Monack, Denise M |
| Thesis advisor | Relman, David A |
| Thesis advisor | Sarnow, P. (Peter) |
| Advisor | Monack, Denise M |
| Advisor | Relman, David A |
| Advisor | Sarnow, P. (Peter) |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Madeleine Moule. |
|---|---|
| Note | Submitted to the Department of Microbiology and Immunology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2010. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2010 by Madeleine Grace Moule
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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