Francisella tularensis

Francisella tularensis is a pathogenic species of Gram-negative coccobacillus, an aerobic bacterium. It is nonspore-forming, nonmotile, and the causative agent of tularemia, the pneumonic form of which is often lethal without treatment. It is a fastidious, facultative intracellular bacterium, which requires cysteine for growth. Due to its low infectious dose, ease of spread by aerosol, and high virulence, F. tularensis is classified as a Tier 1 Select Agent by the U.S. government, along with other potential agents of bioterrorism such as Yersinia pestis, Bacillus anthracis, and Ebola virus. When found in nature, Francisella tularensis can survive for several weeks at low temperatures in animal carcasses, soil, and water. In the laboratory, F. tularensis appears as small rods (0.2 by 0.2 µm), and is grown best at 35-37°C. This species was discovered in ground squirrels in Tulare County, California, in 1911; Bacterium tularense was soon isolated by George Walter McCoy (1876–1952) of the US Plague Lab in San Francisco and reported in 1912. In 1922, Dr. Edward Francis (1872–1957), a physician and medical researcher from Ohio, discovered that Bacterium tularense was the causative agent of tularemia, after studying several cases of his patients having symptoms of the said disease. Later, it became known as 'Francisella tularensis', in honor of the discovery by Dr. Francis. Four subspecies (biovars) of F. tularensis have been classified: In 1938, Soviet bacteriologist Vladimir Dorofeev (1911–1988) and his team were able to recreate the infectious cycle of the pathogen in humans, and his team was the first in the world to create measures in protection against the deadly infectious agent. In 1947, Dorofeev was able to independently isolate the pathogen that Dr. Francis discovered in 1922; hence, it is commonly known as Francisella dorofeev in former Soviet countries. F. tularensis has been reported in birds, reptiles, fish, invertebrates, and mammals including humans. Despite this, no case of tularemia has been shown to be initiated by human-to-human transmission. Rather, it is caused by contact with infected animals or vectors such as ticks, mosquitos, and deer flies. Reservoir hosts of importance can include lagomorphs (e.g. rabbits), rodents, galliform birds, and deer. 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 and conjunctival infection due to inoculation at the eye. F. tularensis is capable of surviving outside of a mammalian host for weeks at a time 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'. Recent epidemiological studies have shown a positive correlation between occupations involving the above activities and infection with F. tularensis. 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 to initiate new rounds of infection. The virulence mechanisms for F. tularensis have not been well characterized. Like other intracellular bacteria that break out of phagosomal compartments to replicate in the cytosol, F. tularensis 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 Francisella, its role as a virulence factor is under vigorous debate.