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. Typhoid fever is a severe systemic illness which is mostly a problem in the developing world and in travelers. Non-typhoidal salmonella infections are increasing in the USA and are largely associated with contaminated food. Salmonellae infections are most severe in infants, the elderly, and in immunosuppressed individuals. This grant proposes to study 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 Salmonella pathogenicity island II. This grant proposes to further define these proteins, and to study in molecular detail their role in bacterial virulence. This grant will test the hypothesis that these effectors modify the Salmonellae-containing vacuole to promote bacterial replication by altering host endocytic trafficking, inflammatory responses, and the vacuolar actin cytoskeleton. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI048683-07
Application #
7158604
Study Section
Host Interactions with Bacterial Pathogens Study Section (HIBP)
Program Officer
Alexander, William A
Project Start
2001-01-15
Project End
2010-12-31
Budget Start
2007-01-01
Budget End
2007-12-31
Support Year
7
Fiscal Year
2007
Total Cost
$340,275
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