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
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
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
Hicks, Stuart W; Galan, Jorge E (2013) Exploitation of eukaryotic subcellular targeting mechanisms by bacterial effectors. Nat Rev Microbiol 11:316-26
Hannemann, Sebastian; Gao, Beile; Galan, Jorge E (2013) Salmonella modulation of host cell gene expression promotes its intracellular growth. PLoS Pathog 9:e1003668
Hicks, Stuart W; Charron, Guillaume; Hang, Howard C et al. (2011) Subcellular targeting of Salmonella virulence proteins by host-mediated S-palmitoylation. Cell Host Microbe 10:9-20
Spano, Stefania; Liu, Xiaoyun; Galan, Jorge E (2011) Proteolytic targeting of Rab29 by an effector protein distinguishes the intracellular compartments of human-adapted and broad-host Salmonella. Proc Natl Acad Sci U S A 108:18418-23
Hicks, Stuart W; Galan, Jorge E (2010) Hijacking the host ubiquitin pathway: structural strategies of bacterial E3 ubiquitin ligases. Curr Opin Microbiol 13:41-6
Galan, Jorge E (2009) Common themes in the design and function of bacterial effectors. Cell Host Microbe 5:571-9
Patel, Jayesh C; Hueffer, Karsten; Lam, Tukiet T et al. (2009) Diversification of a Salmonella virulence protein function by ubiquitin-dependent differential localization. Cell 137:283-94
Du, Fangyong; Galan, Jorge E (2009) Selective inhibition of type III secretion activated signaling by the Salmonella effector AvrA. PLoS Pathog 5:e1000595

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