Francisella tularensis

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Francisella tularensis
Macrophage Infected with Francisella tularensis Bacteria (5950310835).jpg
Francisella tularensis bacteria (blue) infecting a macrophage (yellow)
Scientific classification
Domain:
Phylum:
Class:
Order:
Family:
Francisellaceae
Genus:
Species:
F. tularensis
Binomial name
Francisella tularensis
(McCoy and Chapin 1912)
Dorofe'ev 1947

Francisella tularensis is a pathogenic species of Gram-negative coccobacillus, an aerobic bacterium. [1] It is non-spore forming, non-motile [2] 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. [3] 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 laboratory, F. tularensis appears as small rods (0.2 by 0.2 µm), and is grown best at 35-37°C. [4]

In biology, a pathogen, in the oldest and broadest sense, is anything that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ.

Coccobacillus

A coccobacillus is a type of bacterium with a shape intermediate between cocci and bacilli. Coccobacilli, then, are very short rods which may be mistaken for cocci.

Tularemia primary bacterial infectious disease that has material basis in Francisella tularensis, which is transmitted by dog tick bite (Dermacentor variabilis), transmitted by deer flies (Chrysops sp) or transmitted by contact with infected animal tissues.

Tularemia, also known as rabbit fever, is an infectious disease caused by the bacterium Francisella tularensis. Symptoms may include fever, skin ulcers, and enlarged lymph nodes. Occasionally, a form that results in pneumonia or a throat infection may occur.

Contents

Subspecies

This species was discovered in ground squirrels in Tulare County, California, in 1911; Bacterium tularense was soon isolated by George Walter McCoy (18761952) of the US Plague Lab in San Francisco and reported in 1912. In 1922, Dr. Edward Francis (18721957), a physician and medical researcher from Ohio, discovered that the "Bacterium Tularense" was the causative agent for tularemia, after studying several cases of his patients having symptoms of the said disease. Later, Bacterium Tularense became known as "Francisella tularensis", in honor of the discovery by Dr. Francis. [5] [6] [7] Four subspecies (biovars) of F. tularensis have been classified.

Tulare County, California County in California, United States

Tulare County is a county in the U.S. state of California. As of the 2010 census, the population was 442,179. Its county seat is Visalia. The county is named for Tulare Lake, once the largest freshwater lake west of the Great Lakes. Drained for agricultural development, the site is now in Kings County, which was created in 1893 from the western portion of the formerly larger Tulare County.

A biovar is a variant prokaryotic strain that differs physiologically or biochemically from other strains in a particular species. Morphovars are those strains that differ morphologically. Serovars are those strains that have antigenic properties that differ from other strains.

  1. The subspecies F. t. tularensis (or type A), found predominantly in North America, is the most virulent of the four known subspecies, and is associated with lethal pulmonary infections. This includes the primary type A laboratory strain, SCHUS4.
  2. Subspecies F. t. holarctica (also known as biovar F. t. palearctica or type B) is found predominantly in Europe and Asia, but rarely leads to fatal disease. An attenuated live vaccine strain of subspecies F. t. holarctica has been described, though it is not yet fully licensed by the Food and Drug Administration as a vaccine. This subspecies lacks the citrulline ureidase activity and ability to produce acid from glucose of biovar F. t. palearctica.
  3. Subspecies F. t. novicida (previously classified as F. novicida [8] ) was characterized as a relatively nonvirulent strain; only two tularemia cases in North America have been attributed to F. t. novicida and these were only in severely immunocompromised individuals.
  4. Subspecies F. t. mediasiatica, is found primarily in central Asia; little is currently known about this subspecies or its ability to infect humans.

In 1938, Soviet bacteriologist Vladimir Dorofeev (19111988) and his team were able to recreate the infection 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. 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.

Pathogenesis

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, tularemia 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.

Fish vertebrate animal that lives in water and (typically) has gills

Fish are gill-bearing aquatic craniate animals that lack limbs with digits. They form a sister group to the tunicates, together forming the olfactores. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish as well as various extinct related groups. Tetrapods emerged within lobe-finned fishes, so cladistically they are fish as well. However, traditionally fish are rendered paraphyletic by excluding the tetrapods. Because in this manner the term "fish" is defined negatively as a paraphyletic group, it is not considered a formal taxonomic grouping in systematic biology, unless it is used in the cladistic sense, including tetrapods. The traditional term pisces is considered a typological, but not a phylogenetic classification.

Vector (epidemiology) agent that carries and transmits an infectious pathogen into another living organism

In epidemiology, a disease vector is any agent who carries and transmits an infectious pathogen into another living organism; most agents regarded as vectors are organisms, such as intermediate parasites or microbes, but it could be an inanimate medium of infection such as dust particles.

Tick order of arachnids

Ticks are small arachnids, typically 3 to 5 mm long, part of the order Parasitiformes. Along with mites, they constitute the subclass Acari. Ticks are ectoparasites, living by feeding on the blood of mammals, birds, and sometimes reptiles and amphibians. Ticks had evolved by the Cretaceous period, the most common form of fossilisation being immersed in amber. Ticks are widely distributed around the world, especially in warm, humid climates.

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.[ citation needed ] 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.[ citation needed ]

Pneumonia Infection of the lungs

Pneumonia is an inflammatory condition of the lung affecting primarily the small air sacs known as alveoli. Typically symptoms include some combination of productive or dry cough, chest pain, fever, and trouble breathing. Severity is variable.

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.

Grassland areas where the vegetation is dominated by grasses (Poaceae)

Grasslands are areas where the vegetation is dominated by grasses (Poaceae); however, sedge (Cyperaceae) and rush (Juncaceae) families can also be found along with variable proportions of legumes, like clover, and other herbs. Grasslands occur naturally on all continents except Antarctica. Grasslands are found in most ecoregions of the Earth. For example, there are five terrestrial ecoregion classifications (subdivisions) of the temperate grasslands, savannas, and shrublands biome (ecosystem), which is one of eight terrestrial ecozones of the Earth's surface.

Hay dried grass, legumes or other herbaceous plants used as animal fodder

Hay is grass, legumes, or other herbaceous plants that have been cut and dried to be stored for use as animal fodder, particularly for large grazing animals raised as livestock, such as cattle, horses, goats, and sheep. However, it is also fed to smaller domesticated animals such as rabbits and guinea pigs. Even pigs may be fed hay, but they do not digest it as efficiently as herbivores.

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 to initiate new rounds of infection.

Phagocytosis An endocytosis process that results in the engulfment of external particulate material by phagocytes. The particles are initially contained within phagocytic vacuoles (phagosomes), which then fuse with primary lysosomes to effect digestion of the par

Phagocytosis is the process by which a cell uses its plasma membrane to engulf a large particle, giving rise to an internal compartment called the phagosome. It is one type of endocytosis.

Phagosome

In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs). A phagosome is formed by the fusion of the cell membrane around a microorganism, a senescent cell or an apoptotic cell. Phagosomes have membrane-bound proteins to recruit and fuse with lysosomes to form mature phagolysosomes. The lysosomes contain hydrolytic enzymes and reactive oxygen species (ROS) which kill and digest the pathogens. Phagosomes can also form in non-professional phagocytes, but they can only engulf a smaller range of particles, and do not contain ROS. The useful materials from the digested particles are moved into the cytosol, and waste is removed by exocytosis. Phagosome formation is crucial for tissue homeostasis and both innate and adaptive host defense against pathogens.

Cytosol the part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes

The cytosol, also known as intracellular fluid (ICF) or cytoplasmic matrix, is the liquid found inside cells. It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into many compartments.

Virulence factors

A tularemia lesion on the dorsal skin of a hand Tularemia lesion.jpg
A tularemia lesion on the dorsal skin of a hand

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. [9] A hemolysin activity, named NlyA, with immunological reactivity to Escherichia coli anti-HlyA antibody, was identified in biovar F. t. novicida. [10] 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.

F. tularensis contains type VI secretion system (T6SS), also present in some other pathogenic bacteria. [11] It also contains a number of ATP-binding cassette (ABC) proteins that may be linked to the secretion of virulence factors. [12] F. tularensis 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 F. tularensis phagosomal breakout and intracellular replication; in its absence, mutant F. tularensis cells die and are degraded by the macrophage. This protein is located in a putative pathogenicity island regulated by the transcription factor MglA.

F. tularensis, 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 F. tularensis pathogenicity.

Genetics

Like many other bacteria, F. tularensis undergoes asexual replication. Bacteria divide into two daughter cells, each of which contains identical genetic information. Genetic variation may be introduced by mutation or horizontal gene transfer.

The genome of F. t. tularensis strain SCHU4 has been sequenced. [13] The studies resulting from the sequencing suggest a number of gene-coding regions in the F. tularensis genome are disrupted by mutations, thus create blocks in a number of metabolic and synthetic pathways required for survival. This indicates F. tularensis has evolved to depend on the host organism for certain nutrients and other processes ordinarily taken care of by these disrupted genes.

The F. tularensis genome contains unusual transposon-like elements resembling counterparts that normally are found in eukaryotic organisms.

Phylogenetics

Much of the known global genetic diversity of F. t. holarctica is present in Sweden. [14] This suggests this subspecies originated in Scandinavia and spread from there to the rest of Eurosiberia.

Use as a biological weapon

When the U.S. biological warfare program ended in 1969, F. tularensis was one of seven standardized biological weapons it had developed. [15]

Diagnosis, treatment, and prevention

F. tularensis colonies on an agar plate Francisella tularensis 01.jpg
F. tularensis colonies on an agar plate
Diagnosis

Infection by F. tularensis is diagnosed by clinicians based on symptoms and patient history, imaging, and laboratory studies.

Treatment

Tularemia is treated with antibiotics, such as aminoglycosides, tetracyclines, or fluoroquinolones. About 15 proteins were suggested which could facilitate drug and vaccine design pipeline. [16]

Prevention

Preventive measures include preventing bites from ticks, flies, and mosquitos; ensuring that all game is cooked thoroughly; refraining from drinking untreated water; using insect repellents; if working with cultures of F. tularensis, in the lab, making sure to wear a gown, impermeable gloves, mask, and eye protection; and when dressing game, making sure to wear impermeable gloves. Also, a live attenuated vaccine is available for individuals who are at high risk for exposure such as laboratory personnel. [17]

Genomics

See also

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References

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  16. Francisella tularensis: In silico Identification of Drug and Vaccine Targets by Metabolic Pathway Analysis J Harati, J Fallah The 6th Conference on Bioinformatics
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