Infections caused by such intracellular pathogens as mycobacteria, Salmonella, and Listeria annually claim millions of lives worldwide. This proposal develops the fruit fly, Drosophila melanogaster as a model organism to study these infections. Mutations in both the host and pathogens will be tested. The fruit fly has been used previously to study innate immune responses to gram positive and negative bacteria as well as fungi. Past work focused only on microorganisms that grow freely in the extracellular space. This proposal describes experiments that will use Drosophila to study intracellular infections of macrophages. Growth characteristics including growth rate, lethality and location will be measured for several bacteria that cause infections of Drosophila macrophages (Mycobacterium marinum, Salmonella typhimurium, Listeria monocytogenes). Drosophila mutants expected to have difficulty fighting intracellular pathogens will be tested for their ability to defend against intracellular infections. Salmonella typhimurium mutants will be tested for their ability to infect the fly, to determine the role bacterial genes play in virulence. These experiments will provide tools to analyze a collection of Drosophila mutants isolated based upon a phenotype that is likely to involve the cellular immune response.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI053080-04
Application #
6983412
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Winter, David B
Project Start
2002-12-01
Project End
2007-11-30
Budget Start
2005-12-01
Budget End
2006-11-30
Support Year
4
Fiscal Year
2006
Total Cost
$388,768
Indirect Cost
Name
Stanford University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Schneider, David S; Ayres, Janelle S (2008) Two ways to survive infection: what resistance and tolerance can teach us about treating infectious diseases. Nat Rev Immunol 8:889-95
Ayres, Janelle S; Freitag, Nancy; Schneider, David S (2008) Identification of Drosophila mutants altering defense of and endurance to Listeria monocytogenes infection. Genetics 178:1807-15
Brandt, Stephanie M; Schneider, David S (2007) Bacterial infection of fly ovaries reduces egg production and induces local hemocyte activation. Dev Comp Immunol 31:1121-30
Shirasu-Hiza, Mimi M; Dionne, Marc S; Pham, Linh N et al. (2007) Interactions between circadian rhythm and immunity in Drosophila melanogaster. Curr Biol 17:R353-5
Pham, Linh N; Dionne, Marc S; Shirasu-Hiza, Mimi et al. (2007) A specific primed immune response in Drosophila is dependent on phagocytes. PLoS Pathog 3:e26
Brennan, Catherine A; Delaney, Joseph R; Schneider, David S et al. (2007) Psidin is required in Drosophila blood cells for both phagocytic degradation and immune activation of the fat body. Curr Biol 17:67-72
Dionne, Marc S; Pham, Linh N; Shirasu-Hiza, Mimi et al. (2006) Akt and FOXO dysregulation contribute to infection-induced wasting in Drosophila. Curr Biol 16:1977-85
Gordon, Michael D; Dionne, Marc S; Schneider, David S et al. (2005) WntD is a feedback inhibitor of Dorsal/NF-kappaB in Drosophila development and immunity. Nature 437:746-9
Brandt, Stephanie M; Dionne, Marc S; Khush, Ranjiv S et al. (2004) Secreted Bacterial Effectors and Host-Produced Eiger/TNF Drive Death in aSalmonella-Infected Fruit Fly. PLoS Biol 2:e418
Mansfield, Bryce E; Dionne, Marc S; Schneider, David S et al. (2003) Exploration of host-pathogen interactions using Listeria monocytogenes and Drosophila melanogaster. Cell Microbiol 5:901-11