acid from glucose of biovar F. t. palearctica. F. t. mediasiatica, is found primarily in central Asia; little is currently known about this subspecies or its ability to infect humans. Additionally, F. novicida has sometimes previously been classified as F. t. novicida. It was characterized as a relatively nonvirulent Francisella; only two tularemia cases in North America have been attributed to the organism, and these were only in severely immunocompromised individuals. Pathogenesis F. tularensis has been reported in invertebrates including insects and ticks, and vertebrates such as birds, amphibians, reptiles, fish and mammals, including humans. Human infection is often caused by vectors, particularly ticks but also mosquitos, deer flies and horse-flies. Direct contact with infected animals or carcasses is another source. Important reservoir hosts include lagomorphs (e.g. rabbits), rodents, galliform birds and deer. Infection via fomites (objects) is also important. Human-to-human transmission has not been demonstrated. F. tularensis can survive for weeks outside a mammalian host and has been found in water, grassland, and haystacks. Aerosols containing the bacteria may be generated by disturbing carcasses due to brush cutting or lawn mowing; as a result, tularemia has been referred to as "lawnmower disease". Epidemiological studies have shown a positive correlation between occupations involving the above activities and infection with F. tularensis. Human infection with F. tularensis can occur by several routes. Portals of entry are through blood and the respiratory system. The most common occurs via skin contact, yielding an ulceroglandular form of the disease. Inhalation of bacteria, particularly biovar F. t. tularensis, leads to the potentially lethal pneumonic tularemia. While the pulmonary and ulceroglandular forms of tularemia are more common, other routes of inoculation have been described and include oropharyngeal infection due to consumption of contaminated food or water, and conjunctival infection due to inoculation at the eye. Lifecycle F. tularensis is a facultative intracellular bacterium that is capable of infecting most cell types, but primarily infects macrophages in the host organism. Entry into the macrophage occurs by phagocytosis and the bacterium is sequestered from the interior of the infected cell by a phagosome. F. tularensis then breaks out of this phagosome into the cytosol and rapidly proliferates. Eventually, the infected cell undergoes apoptosis, and the progeny bacteria are released in a single "burst" event to initiate new rounds of infection. Virulence factors The virulence mechanisms for F. tularensis have not been well characterized. Like other intracellular bacteria that