Yersinia pestis translocate virulence factors from the bacterial cytoplasm into host immune cells during infections through the Type III Secretion System (TTSS). This system allows for rapid activation of injection of Yops, proteins that go on to disable phagocytosis and immune recognition thereby enabling bacterial replication and disease. The TTSS is a tightly coordinated process of expression, assembly of secretion and translocation pores, and injection of effector proteins that responds rapidly to inducing signs indicating contact with a host cell. Accurate timing of these events is critical to optimum performance, allowing Yersinia pestis to establish lethal infections from very small challenge doses. My laboratory is interested in the process of translocation of effector proteins, specifically in how the translocon is inserted in the plasma membrane and how this signals activation of the TTSS. In this work, we seek to gain insight into the activation of the TTSS, by establishing a basic understanding of the molecular mechanism of repression of TTSS genes in the absence of host cell contact and through the identification of genes that are directly regulated through this mechanism. Results of the proposed investigations will provide preliminary data on which we can build a program that investigates molecular events of activation of the TTSS in vivo as well as in vitro, studies which may provide insight into the molecular mechanisms of Yersinia pestis pathogenesis.

Public Health Relevance

This proposal investigates the mechanism of regulation of the type III secretion system in Yersinia pestis, the causative agent of plague. The goal is to establish the molecular mechanism of activation of the TTSS in response to contact with host immune cells in order to study the role of this process in the development of plague.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI081035-01A1
Application #
7739891
Study Section
Special Emphasis Panel (ZRG1-IDM-A (90))
Program Officer
Mukhopadhyay, Suman
Project Start
2009-06-19
Project End
2011-05-31
Budget Start
2009-06-19
Budget End
2010-05-31
Support Year
1
Fiscal Year
2009
Total Cost
$183,751
Indirect Cost
Name
University of Missouri-Columbia
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
153890272
City
Columbia
State
MO
Country
United States
Zip Code
65211