<unk>  has been reported in invertebrates including insects and ticks, 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.<unk>  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<unk> . Human infection with<unk>  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.<unk> , 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<unk>  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.<unk>  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 A tularemia lesion on the dorsal skin of a hand The virulence mechanisms for<unk>  have not been well characterized. Like other intracellular bacteria that break out of phagosomal compartments to replicate in the cytosol,<unk>  strains produce different hemolytic agents, which may facilitate degradation of the phagosome. A hemolysin activity, named NlyA, with immunological reactivity to Escherichia coli anti-HlyA antibody, was identified in biovar F. t. novicida. Acid phosphatase AcpA has been found in other bacteria to act as a hemolysin, whereas in<unk> , its role as a virulence factor is under vigorous debate.<unk>  contains type VI secretion system (T6SS), also present in some other pathogenic bacteria. It also contains a number of ATP-binding cassette (ABC) proteins that may be linked to the secretion of virulence factors.<unk>  uses type IV pili to bind to the exterior of a host cell and thus become phagocytosed. Mutant strains lacking pili show severely attenuated pathogenicity. The expression of a 23-kD protein known as IglC is required for<unk>  phagosomal breakout and intracellular replication; in its absence, mutant<unk>  cells die and are degraded by the macrophage. This protein is located in a putative pathogenicity island regulated by the transcription factor MglA.<unk> , in vitro, downregulates the immune response of infected cells, a tactic used by a significant number of pathogenic organisms to ensure their replication is (albeit briefly) unhindered by the host immune system by blocking the warning signals from the infected cells. This downmodulation of the immune response requires the IglC protein, though again the contributions of IglC and other genes are unclear. Several other putative virulence genes exist, but have yet to be characterized for function in<unk>  pathogenicity.
Francisella tularensis
Yersinia pestis
Kingella kingae
Bacillus anthracis
Edwardsiella 
Salmonella enterica subsp. enterica
Listeria monocytogenes
Vibrio vulnificus