Francisella tularensis is one of the most infectious organisms as inhalation of a single bacterium can lead to a fatal disease referred to as tularemia. It has therefore been categorized by the Centers for Disease Control and Prevention as a Category A biodefense agent. Many seminal studies have shown that the ability of F. tularensis to replicate within macrophages is a feature of this organism during infection. Only recently we have appreciated that interactions with non-macrophages are also extremely important during infection as these cells provide a niche for immune protection, proliferation, and other unexplored roles. Although much of the work in the field of F. tularensis has focused on the intra-macrophage biology of this organism, interactions with other cell types have not been thoroughly investigated. Using both in vivo and in vitro approaches, we present strong evidence that F. tularensis invades and persists in erythrocytes. The proposed work will provide an understanding of a previously uncharacterized phenomenon by a Category A biodefense agent - namely erythrocyte invasion by F. tularensis. The two aims to investigate erythrocyte invasion by F. tularensis are: 1) To examine the molecular mechanism of F. tularensis erythrocyte invasion. 2) To determine the role of erythrocyte invasion by F. tularensis. As erythrocyte invasion of F. tularensis has not yet been described in the literature, the studies proposed here will open up a new line of research. We will investigate a potential role in pathogenesis, arthropod transmission, and disease persistence. Our work will involve evaluation of fixed blood from tularemia patients to assess the degree of erythrocyte invasion during human infection. We will also examine the mechanism by which F. tularensis erythrocyte invasion occurs, exposing novel host-microbe molecular pathways. In addition to enhancing our understanding of an important Category A biodefense agent, the research proposed may also uncover general systems implemented by diverse intracellular pathogens. The bacterial pathogen Francisella tularensis is a signficant bioterror threat. The research descibed in this proposal will make important advances toward understanding how this organism invades red blood cells. The results of this work may lead to vaccine development and potential therapeutics that alter the Francisella- erythrocytre interactions.

Public Health Relevance

The bacterial pathogen Francisella tularensis is a signficant bioterror threat. The research descibed in this proposal will make important advances toward understanding how this organism invades red blood cells. The results of this work may lead to vaccine development and potential therapeutics that alter the Francisella-erythrocytre interactions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Career Transition Award (K22)
Project #
1K22AI087703-01A1
Application #
8041250
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Program Officer
Mukhopadhyay, Suman
Project Start
2012-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
1
Fiscal Year
2012
Total Cost
$157,920
Indirect Cost
$7,920
Name
West Liberty University
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
928338607
City
West Liberty
State
WV
Country
United States
Zip Code
26074