Anders Sjöstedt

The bacterium today known as Francisella tularensis was first identified 99 years ago and, since then, much research has been devoted to study it and the resulting disease, tularemia. F. tularensis became the focus of an intense research effort during the first half of the 20th century, in particularly in the United States and Soviet Union, since the disease was fairly common. Due to its high infectivity, ease of spread, and severity of the resulting disease, it was one of the agents given the highest priority in the biological weapon programs of the United States and Soviet Union. After termination of these programs in the 1960s, the interest in F. tularensis diminished significantly, but after several decades of little attention, the last decade has led to resurgence in the research on F. tularensis. In 2003, the Science magazine phrased it as follows: “an obscure weapon of the cold war edges into the limelight”. There were multiple reasons for this resurgence, one of which was an increase in the number of tularemia cases in several European countries and, moreover, the intense research effort on potential bioterrorist agents in the US post 9/11. Thereby, the number of annual publications on F. tularensis has tripled in 10 years, and many new research groups, in particular American, have entered the field. This has led to very rapid development of state-of-the-art research tools, and fast progress in the understanding of F. tularensis. A proof of the rapid progress was the publication of a comprehensive volume on Francisella and tularemia in 2007. Although only four years ago, the rapid pace of the research has led to many new discoveries since then and, to this end, we now present a collection of articles from leading scientists on the up-to-date knowledge regarding F. tularensis. The articles cover important areas such as molecular research tools, experimental models, genomics, virulence mechanisms, manipulation and subversion of host responses, host immune responses, and the ecology of F. tularensis.

Francisella tularensis and tularemia

Anders Johansson

Thomas Henry

Marina Santic

Jiri Stulik

Max Maurin

Joseph Wayne Conlan

Tularemia is a severe anthropozoonosis caused by Francisella tularensis. The genus Francisella contains five species: F. tularensis, F. philomiragia, F. hispaniensis, F. noatunensis and F. novicida. First described in 1911 in Tulare County, California, it has since been reported worldwide, capable of infecting more than 250 vertebrates and invertebrate species. Although it causes disease in various animal species, no animal has been identified as a main reservoir of this pathogen. Humans acquire infection by several routes, including direct contact with infected animals, ingestion of water or food contaminated by infected animals, exposure to infected arthropod vectors or by inhalation of infective aerosols resulting in pneumonic, oropharyngeal, glandular, ulceroglandular or oculoglandular tularemia. The clinical presentation of human tularemia depends on route of the infection, the causative Francisella strain, and the immune response of the host. A live attenuated vaccine (LVS) has been available for more than 50 years, however, unlikely to become licensed in the future due to a lack of understanding of the genetic basis for its attenuation. Due to the ease of its dissemination, its multiple routes of infection, its low dose of infection, severe morbidity, and high rate of mortality, F. tularensis subsp. tularensis has been classified as a category A bioterrorism agent by the CDC. Many virulence factors of F. tularensis have been discovered and investigated, but more in-depth host pathogen interaction analyses are needed to define mechanisms of pathogenicity and virulence of this unique pathogen.

Anders Sjöstedt

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