About the Project
Francisella tularensis colonization on Cysteine Heart Agar after 72 hours. Obtained from the CDC Public Health Image Library. Image credit: CDC/Larry Stauffer, Oregon State
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F. tularensis, a small, nonmotile, nonsporulating, gram-negative, coccobacillus is currently one of the most infectious bacteria known and is the causative agent of the systemic disease tularemia, a potentially severe and fatal disease in humans. F. tularensis is also characterized by its resilience to environmental conditions and its ease of dissemination. For these reasons, F. tularensis poses a serious threat to laboratory workers who handle the organism and is a bioterrorism concern.
The gamma-protobacterial family Francisellaceae consists of two genera: Francisella tularensis and Francisella philomiragia. F. tularensis has four subspecies: tularensis (Type A), holarctica (Type B), mediaasiatica (geographically restricted to the central Asia) and novicida (a rare isolate initially isolated from a water source in Utah in 1951). F. tularensis subsp. tularensis, is the most virulent subspecies and is geographically restricted to the North American continent, with only one report of isolation of Type A in Europe. Subspecies holarctica is moderately virulent and is found throughout the Northern hemisphere including the Scandinavian countries, Russia, Spain, Japan and the U. S. Because the subspecies are very similar, diagnostic microbiological identification has relied on differences in virulence and in a small number of non-routine biochemical/DNA assays (e.g. PCR-based DNA fingerprinting analyses).
The subsp. holarctica live attenuated vaccine strain (LVS) is currently the only effective vaccine against tularemia. The vaccine is approved in the U.S. only for use in clinical trials, and its future availability is undetermined because the protective response offered by the vaccine has not been well characterized, the basis of its attenuation is unknown, and LVS is fully virulent when delivered intraperitoneally in mice. The fact that the LVS provides protective immunity suggests that efforts to create a defined attenuated mutant may be fruitful, however such strains may not be available for some time.
RC503 has been historically used as a virulent Type B murine challenge strain by Russian scientists. The sequence data from this genome will serve as a comparative reference to aid in the identification of potentially attenuating mutations in the LVS and will provide further data toward identifying the genetic determinants that distinguish Type B pathogenicity and geographic distribution.
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