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Tularaemia: bioterrorism defence renews interest in Francisella tularensis

Nature Reviews Microbiology volume 2, pages 967–978 (2004)Cite this article

Key Points

  • Tularaemia is a highly infectious pathogen that is capable of causing a fatal disease, notably with doses that contain as few as 25 colony-forming units. This has made the organism that causes tularaemia, Francisella tularensis, attractive for use in biological weapons programmes.

  • Although a live vaccine strain has been used for many decades to immunize several thousand individuals, this vaccine is not licensed and is unlikely to prove licensable given current regulatory constraints. There is a need to develop a safe and licensable vaccine to protect against tularemia, particularly the pneumonic form of the disease.

  • F. tularensis is an intracellular pathogen that multiplies within macrophages and amoebae, resulting in high titres of bacteria. However, little is known about the mechanisms that this bacterium uses to adapt to and exploit the intracellular environment.

  • The epidemiology and geographical incidence of F. tularensis, and the typical clinical features of the disease — which can depend on the route of infection — are reviewed here.

  • The availability of genome sequence data for the vaccine strain and a virulent isolate of F. tularensis should facilitate development of a new vaccine. However, progress is still hampered by a lack of genetic tools for F. tularensis.

  • Approaches to develop a new vaccine might involve the identification of a specific subunit for use in a vaccine, or the production of a live attenuated strain. However, subunits must be delivered in a suitable conformation to induce a protective immune response.

Abstract

Francisella tularensis is a highly infectious aerosolizable intracellular pathogen that is capable of causing a debilitating or fatal disease with doses as low as 25 colony-forming units. There is no licensed vaccine available. Since the 1950s there has been concern that F. tularensis could be used as a biological threat agent, and it has received renewed attention recently owing to concerns about bioterrorism. The International Conference on Tularaemia in 2003 attracted more than 200 delegates, twice the number of participants as previous meetings. This is a reflection of the increased funding of research on this pathogen, particularly in the United States.

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Figure 1: Features of Francisella tularensis.
Figure 2: Worldwide incidence map of the four main Francisella subspecies.
Figure 3: A tularaemia lesion on the dorsal skin of the right-hand, caused by the bacterium Francisella tularensis (1963).
Figure 4: The intracellular lifestyle of F. tularensis.

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Authors and Affiliations

  1. Dstl Porton Down, Salisbury, SP4 0JQ, Wiltshire, UK

    Petra C.F. Oyston & Richard W. Titball

  2. Department of Clinical Microbiology, Umeå University, Umeå, Sweden

    Anders Sjöstedt

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  1. Petra C.F. Oyston
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Correspondence to Petra C.F. Oyston.

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DATABASES

Infectious Disease Information

tularemia

FURTHER INFORMATION

LVS genome sequence

SchuS4 genome sequence

Legionella pneumophila genome sequence

1972 Convention on the prohibition of the development, production and stockpiling of bacteriological (biological) and toxin weapons and their destruction

Glossary

ENZOOTIC

Relating to a zoonotic infection, usually used in the context of a geographical area.

ZOONOSIS

An infection that is transmitted between lower vertebrates and humans.

LAGOMORPH

Any placental mammal with furred feet and two pairs of upper incisors that are specialized for gnawing, such as hares, rabbits and pikas.

SUPPURATION

The formation or discharge of pus. An abscess is a localized area of suppuration.

MACROPHAGE

A cell of the mononuclear phagocyte system that is responsible for phagocytosis of foreign material.

PHAGOSOME

A vesicle that is formed by invagination of plasma membranes during endocytosis. Vesicles containing lysozyme then fuse with the phagosome to degrade engulfed material.

CYTOKINES

Small proteins that are important for immunity and inflammation and that act on effector cells of the immune system.

OTOTOXICITY

Having a toxic effect on the structures of the ear, especially on its nerve supply.

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Oyston, P., Sjöstedt, A. & Titball, R. Tularaemia: bioterrorism defence renews interest in Francisella tularensis. Nat Rev Microbiol 2, 967–978 (2004). https://doi.org/10.1038/nrmicro1045

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