Salmonellosis continues to be a major worldwide health concern. Essential to the pathogenicity of these bacteria is the coordinated activities of two type III protein secretion systems (TTSS), which direct the translocation into host cells of a battery of bacterial effector proteins that modulate a variety of cellular processes. 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, and in particular the study of the function of several Salmonella TTSS effector proteins. This research project is aimed at deepening our understanding of the cell biology of the Salmonella/host interactions, and the function of TTSS effector proteins whose role in the infection process is poorly understood. It is hoped that these studies will facilitate the development of novel immunological and pharmacological strategies to prevent diseases caused by all Salmonella enterica serovars. Furthermore, the paradigms of host-pathogen interactions established by these studies may also help the understanding of the pathogenesis of other important pathogens, which have evolved close associations with their hosts.

Public Health Relevance

Salmonella enterica, which causes food poisoning and typhoid fever in humans, continues to be a very significant health problem. It is estimated that there are 1.3 billion cases of Salmonella infections every year leading to 3 million annual deaths. Knowledge gained from this research should help develop novel therapeutic and prevention strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI055472-19
Application #
8260423
Study Section
Host Interactions with Bacterial Pathogens Study Section (HIBP)
Program Officer
Alexander, William A
Project Start
1995-05-01
Project End
2013-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
19
Fiscal Year
2012
Total Cost
$572,334
Indirect Cost
$226,513
Name
Yale University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Sun, Hui; Kamanova, Jana; Lara-Tejero, Maria et al. (2016) A Family of Salmonella Type III Secretion Effector Proteins Selectively Targets the NF-κB Signaling Pathway to Preserve Host Homeostasis. PLoS Pathog 12:e1005484
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
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
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; Lara-Tejero, Maria; Marlovits, Thomas C et al. (2014) Bacterial type III secretion systems: specialized nanomachines for protein delivery into target cells. Annu Rev Microbiol 68:415-38
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
Hannemann, Sebastian; Gao, Beile; Galán, Jorge E (2013) Salmonella modulation of host cell gene expression promotes its intracellular growth. PLoS Pathog 9:e1003668
Hicks, Stuart W; Galan, Jorge E (2013) Exploitation of eukaryotic subcellular targeting mechanisms by bacterial effectors. Nat Rev Microbiol 11:316-26
Spanò, Stefania; Galán, Jorge E (2013) A novel anti-microbial function for a familiar Rab GTPase. Small GTPases 4:252-4
Spanò, Stefania; Galán, Jorge E (2012) A Rab32-dependent pathway contributes to Salmonella typhi host restriction. Science 338:960-3

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