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Pathogen Page

Francisella tularensis

I. General Information

1. NCBI Taxonomy ID:

2. Disease:

Tularemia

3. Introduction

Francisella tularensis is the etiologic agent of tularemia, a zoonotic disease of which there are several recognized forms depending upon the route of entry of bacteria into the host. These forms include ulceroglandular, glandular, typhoidal, occuloglandular, gastrointestinal and oropharyngeal tularemia. Of these, ulceroglandular tularemia is the most common, with general flu-like symptoms often described. An ulcer at the site of infection is observed, which may persist for up to several months. The lymphatic system disseminates bacteria from the initial infection site and the resultant colonization of the draining lymph nodes leads to swelling; the swollen lymph node resembles the "bubo", a classic symptom of bubonic plague. The most severe form of the disease is the pneumonic form. Primary cases of pneumonic tularemia are generally associated with the disturbance of contaminated dust, for example following the handling of hay or straw which has previously been soiled by infected rodents.

4. Microbial Pathogenesis

There are two types of F. tularensis; Type A is the most virulent causing an often fatal disease while Type B is less virulent and therefore causes a milder form of disease. The species are classified into four distinct sub-species. F. tularensis subspecies tularensis comprises all the strains previously classified as Type A. F. tularensis subspecies holarctica comprises those strains classically referred to as Type B. F. tularensis subspecies mediaasiatica comprises Central Asian strains. The fourth subspecies, F. tularensis subspecies novicida, is a very infrequent cause of human disease, although F. novicida is able to cause a lethal infection in the murine model of disease (Isherwood et al., 2005).

Link to pathogenesis of Francisella tularensis in HazARD.

5. Host Ranges and Animal Models

F. tularensis is the etiologic agent of tularemia, a zoonotic disease that affects a range of animals, including rabbits, hares and rodents. Human disease occurs throughout the northern hemisphere (Isherwood et al., 2005).

6. Host Protective Immunity

While antibody develops against both lipopolysaccharide (LPS) and protein antigens, the role of antibody in protection depends on the nature of the challenge strain. In the murine model of disease, immunization with LPS is able to provide antibody-mediated protection against an otherwise lethal intradermal or intraperitoneal challenge with F. tularensis subspecies holarctica. However, similarly immunized mice are only partially protected against an airborne challenge with F. tularensis subspecies holarctica. When challenged with the most virulent strains of F. tularensis (subspecies tularensis) by any routes, there is at best evidence only of a slight delay in the time to death.

Cellular immunity is likely to play the main role in protection against tularemia. In mice challenged with F. tularensis LVS, neither CD4+ nor CD8+ T cells appear to be absolutely required for control of the infection, but either cell type can promote clearance of the challenge. However, both CD4+ and CD8+ T cells appear to be required for the clearance of a challenge with F. tularensis subspecies tularensis. The clearance of F. tularensis is likely due to the Th1-related cytokines TNFα, IFNγ, and IL-12.

Overall, protection against tularemia is likely to be dependent on the induction of antibody, CD4+ and CD8+ T cell immune responses. The induction of all of these responses appears to be necessary for protection and effective clearance of the most virulent strains (Isherwood et al., 2005).

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