Salmonellosis continues to be a major worldwide health concern. Essential to the pathogenicity of these bacteria is a type III protein secretion system (TTSS) encoded within a pathogenicity island (SPI-1) located at centisome 63. This system directs the translocation into host cells of a battery of bacterial effector proteins that stimulate a variety of cellular responses. These responses are critical for pathogenicity as they allow the bacteria to gain access to host cells, avoid host defense mechanisms and reach deeper tissues. Work in our laboratory supported by this Grant has focused on the study of the cell biology of the complex functional interface between Salmonella enterica and host cells. The proposed research project is aimed at gaining a better understanding of the cell biology of the Salmonella host interactions and the function of several SPI-1 TTSS effector proteins whose role in the infection process is poorly understood. More specifically, we propose: 1) To elucidate cellular events that lead to Salmonella-induced actin polymerization and bacterial entry; 2) To investigate the role of the SP1-TTSS effector protein SopB in the formation of the Salmonella-containing macropinosomes; 3) To investigate the effector function of the SPI-1 TTSS secreted protein SipB; and 4) To investigate the potential role of the SPI-1 TTSS in the interaction of Salmonella with the innate immune system. These studies will advance the understanding of the cell biology of Salmonella enterica infections and that of other important pathogens that have evolved close associations with their hosts. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI055472-13
Application #
7061193
Study Section
Special Emphasis Panel (ZRG1-BM-1 (02))
Program Officer
Alexander, William A
Project Start
1995-05-01
Project End
2008-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
13
Fiscal Year
2006
Total Cost
$555,362
Indirect Cost
Name
Yale University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Galán, Jorge E; Waksman, Gabriel (2018) Protein-Injection Machines in Bacteria. Cell 172:1306-1318
Sun, Hui; Kamanova, Jana; Lara-Tejero, Maria et al. (2018) Salmonella stimulates pro-inflammatory signalling through p21-activated kinases bypassing innate immune receptors. Nat Microbiol 3:1122-1130
Spanò, Stefania; Galán, Jorge E (2018) Taking control: Hijacking of Rab GTPases by intracellular bacterial pathogens. Small GTPases 9:182-191
Fowler, Casey C; Chang, Shu-Jung; Gao, Xiang et al. (2017) Emerging insights into the biology of typhoid toxin. Curr Opin Microbiol 35:70-77
Hannemann, Sebastian; Galán, Jorge E (2017) Salmonella enterica serovar-specific transcriptional reprogramming of infected cells. PLoS Pathog 13:e1006532
Spanò, Stefania; Gao, Xiang; Hannemann, Sebastian et al. (2016) A Bacterial Pathogen Targets a Host Rab-Family GTPase Defense Pathway with a GAP. Cell Host Microbe 19:216-26
Sun, Hui; Kamanova, Jana; Lara-Tejero, Maria et al. (2016) A Family of Salmonella Type III Secretion Effector Proteins Selectively Targets the NF-?B Signaling Pathway to Preserve Host Homeostasis. PLoS Pathog 12:e1005484
Kamanova, Jana; Sun, Hui; Lara-Tejero, Maria et al. (2016) The Salmonella Effector Protein SopA Modulates Innate Immune Responses by Targeting TRIM E3 Ligase Family Members. PLoS Pathog 12:e1005552
Galán, Jorge E (2016) Typhoid toxin provides a window into typhoid fever and the biology of Salmonella Typhi. Proc Natl Acad Sci U S A 113:6338-44
Kohler, Amanda C; Spanò, Stefania; Galán, Jorge E et al. (2014) Structural and enzymatic characterization of a host-specificity determinant from Salmonella. Acta Crystallogr D Biol Crystallogr 70:384-91

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