Francisella tularensis is an extremely virulent Gram negative, facultative intracellular bacterial pathogen capable of causing rapidly progressing lethal infections in literally hundreds of diverse animal species, including humans. Although the general properties of Francisella virulence and pathogenesis are understood, the function of any one Francisella protein not assured by sequence homology remains essentially unknown. This situation is due, in part, to the fact that most open reading frames in Francisella have no known orthologs. Our goal is to uncover and experimentally determine unknown mechanisms and properties that contribute to virulence and pathogenesis. Herein we propose to define the function of RipA, which is a cytoplasmic membrane protein that is conserved among Francisella and is required for adaptation to the host cell environment. This goal will be accomplished through genetic and phenotypic analysis of ripA mutants and extragenic suppressors of ripA mutant phenotypes, identification of RipA - binding proteins, biophysical studies on RipA topology and structure, and regulation of ripA expression.

Public Health Relevance

We are focused on understanding the bacterial properties of Francisella tularensis that make this organism such a highly virulent pathogen for humans, particularly with respect to pulmonary disease. In this application we will study the biological properties of a limited number of cellular components that are unique to Francisella and determine their contribution to Francisella virulence and pathogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI082870-04
Application #
8513890
Study Section
Special Emphasis Panel (ZRG1-IDM-M (02))
Program Officer
Mukhopadhyay, Suman
Project Start
2010-08-16
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
4
Fiscal Year
2013
Total Cost
$340,471
Indirect Cost
$107,821
Name
University of North Carolina Chapel Hill
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Miller, Cheryl N; LoVullo, Eric D; Kijek, Todd M et al. (2013) PanG, a new ketopantoate reductase involved in pantothenate synthesis. J Bacteriol 195:965-76
Mortensen, Brittany L; Fuller, James R; Taft-Benz, Sharon et al. (2012) Francisella tularensis RipA protein topology and identification of functional domains. J Bacteriol 194:1474-84