Abstract

Salmonella are facultative intracellular pathogens which cause significant diseases in humans and animals. These organisms cause several disease syndromes, including enteric (typhoid) fever, gastroenteritis, bacteremias and focal infections. This grant proposes to study a murine infection with S. typhimurium and infection of macrophages and cultured epithelial cells with S. typhimurium and S. typhi. A set of virulence genes, termed Salmonella translocated effectors, that are translocated across the phagosome membrane into the eukaryotic cell cytoplasm by a type III secretion system encoded on the Salmonella pathogenicity island II will be studied. This grant proposes to further define these proteins and to study in molecular detail their role in virulence.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI048683-04
Application #
6691075
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Alexander, William A
Project Start
2001-01-15
Project End
2005-12-31
Budget Start
2004-01-01
Budget End
2004-12-31
Support Year
4
Fiscal Year
2004
Total Cost
$301,136
Indirect Cost

  Institution

Name
University of Washington
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

LaRock, Doris L; Chaudhary, Anu; Miller, Samuel I (2015) Salmonellae interactions with host processes. Nat Rev Microbiol 13:191-205
Kolodziejek, Anna M; Miller, Samuel I (2015) Salmonella modulation of the phagosome membrane, role of SseJ. Cell Microbiol 17:333-41
Pultz, Ingrid Swanson; Christen, Matthias; Kulasekara, Hemantha Don et al. (2012) The response threshold of Salmonella PilZ domain proteins is determined by their binding affinities for c-di-GMP. Mol Microbiol 86:1424-40
LaRock, Doris L; Brzovic, Peter S; Levin, Itay et al. (2012) A Salmonella typhimurium-translocated glycerophospholipid:cholesterol acyltransferase promotes virulence by binding to the RhoA protein switch regions. J Biol Chem 287:29654-63
Mills, Erez; Pultz, Ingrid S; Kulasekara, Hemantha D et al. (2011) The bacterial second messenger c-di-GMP: mechanisms of signalling. Cell Microbiol 13:1122-9
Vinh, Dani B N; Ko, Dennis C; Rachubinski, Richard A et al. (2010) Expression of the Salmonella spp. virulence factor SifA in yeast alters Rho1 activity on peroxisomes. Mol Biol Cell 21:3567-77
Levin, Itay; Eakin, Catherine; Blanc, Marie-Pierre et al. (2010) Identification of an unconventional E3 binding surface on the UbcH5 ~ Ub conjugate recognized by a pathogenic bacterial E3 ligase. Proc Natl Acad Sci U S A 107:2848-53
Christen, Matthias; Coye, Lisette H; Hontz, Jill S et al. (2009) Activation of a bacterial virulence protein by the GTPase RhoA. Sci Signal 2:ra71
Ohlson, Maikke B; Huang, Zhiwei; Alto, Neal M et al. (2008) Structure and function of Salmonella SifA indicate that its interactions with SKIP, SseJ, and RhoA family GTPases induce endosomal tubulation. Cell Host Microbe 4:434-46
Wasylnka, Julie A; Bakowski, Malina A; Szeto, Jason et al. (2008) Role for myosin II in regulating positioning of Salmonella-containing vacuoles and intracellular replication. Infect Immun 76:2722-35

Showing the most recent 10 out of 19 publications