The goal of this research proposal is to identify virulence factors in Francisella tularensis Schu S4. In nature, F. tularensis causes the zoonotic disease tularemia. F. tularensis is a category A select agent because of its highly infectious nature and the potential ease of its dissemination by aerosolization. Worldwide terrorist activities have resulted in growing concerns about the potential use of F. tularensis as a bioterrorist weapon;in response, the National Institute of Allergy and Infectious Diseases has expanded its biodefense research program in an effort to develop new F. tularensis therapeutics and vaccines. The long-term goal of the proposed research is to identify novel targets for the development of therapeutics for the treatment of tularemia. We will use a genetic approach to identify F. tularensis genes that are specifically expressed during growth in host cells. In accordance with our research goals, three scientific aims are proposed.
In specific aim 1 a genomic library will be constructed.
In specific aim 2 the genomic library will be screened for in vivo expressed genes and in specific aim 3 null mutants in in vivo expressed genes will be tested in an animal model of tularemia. The results of the proposed work will provide numerous leads for drug discovery, cell biology experiments, and microbiological experiments.

Public Health Relevance

This research project is focused on defining the mechanism by which Francisella tularensis causes the disease tularemia.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1-IDM-A (90))
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Mukhopadhyay, Suman
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University of Tennessee Health Science Center
Other Basic Sciences
Schools of Medicine
United States
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Miller, Mark A; Stabenow, Jennifer M; Parvathareddy, Jyothi et al. (2012) Visualization of murine intranasal dosing efficiency using luminescent Francisella tularensis: effect of instillation volume and form of anesthesia. PLoS One 7:e31359
Jayakar, Himangi R; Parvathareddy, Jyothi; Fitzpatrick, Elizabeth A et al. (2011) A galU mutant of Francisella tularensis is attenuated for virulence in a murine pulmonary model of tularemia. BMC Microbiol 11:179
Llewellyn, Anna C; Jones, Crystal L; Napier, Brooke A et al. (2011) Macrophage replication screen identifies a novel Francisella hydroperoxide resistance protein involved in virulence. PLoS One 6:e24201
Bina, Xiaowen R; Miller, Mark A; Bina, James E (2010) Construction of a bioluminescence reporter plasmid for Francisella tularensis. Plasmid 64:156-61
Clinton, Shawn R; Bina, James E; Hatch, Thomas P et al. (2010) Binding and activation of host plasminogen on the surface of Francisella tularensis. BMC Microbiol 10:76