|Francisella tularensis bacteria (blue) infecting a macrophage (yellow)|
(McCoy and Chapin 1912)
Francisella tularensis is a pathogenic species of Gram-negative coccobacillus, an aerobic bacterium. µm), and is grown best at 35-37°C.It is non-spore forming, non-motile 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 laboratory, F. tularensis appears as small rods (0.2 by 0.2
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.
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, 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.
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 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. Four subspecies (biovars) of F. tularensis have been classified.
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.
In 1938, Soviet bacteriologist Vladimir Dorofeev (1911–1988) 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.
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 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.
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.
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 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.
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 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.
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 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.
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.
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.
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.
F. tularensis 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. 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.
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.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.
Much of the known global genetic diversity of F. t. holarctica is present in Sweden.This suggests this subspecies originated in Scandinavia and spread from there to the rest of Eurosiberia.
When the U.S. biological warfare program ended in 1969, F. tularensis was one of seven standardized biological weapons it had developed.
Infection by F. tularensis is diagnosed by clinicians based on symptoms and patient history, imaging, and laboratory studies.
Tularemia is treated with antibiotics, such as aminoglycosides, tetracyclines, or fluoroquinolones. About 15 proteins were suggested which could facilitate drug and vaccine design pipeline.
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.
Yersinia pestis is a gram-negative, nonmotile, rod-shaped coccobacillus bacteria, with no spores. It is a facultative anaerobic organism that can infect humans via the Oriental rat flea. It causes the disease plague, which takes three main forms: pneumonic, septicemic and bubonic plagues. All three forms were responsible for a number of high-mortality epidemics throughout human history, including: the sixth century's Plague of Justinian; the Black Death, which accounted for the death of at least one-third of the European population between 1347 and 1353; and the Third Pandemic, sometimes referred to as the Modern Plague, which began in the late nineteenth century in China and spread by rats on steamboats claiming close to 10,000,000 lives. These plagues likely originated in China and were transmitted west via trade routes. Recent research indicates that the pathogen may have been the cause of what is described as the Neolithic Decline, when European populations declined significantly. This would push the date to much earlier and might be indicative of an origin in Europe rather than Eurasia.
Escherichia coli, also known as E. coli, is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus Escherichia that is commonly found in the lower intestine of warm-blooded organisms (endotherms). Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in their hosts, and are occasionally responsible for product recalls due to food contamination. The harmless strains are part of the normal microbiota of the gut, and can benefit their hosts by producing vitamin K2, and preventing colonization of the intestine with pathogenic bacteria, having a symbiotic relationship. E. coli is expelled into the environment within fecal matter. The bacterium grows massively in fresh fecal matter under aerobic conditions for 3 days, but its numbers decline slowly afterwards.
Streptococcus pyogenes is a species of Gram-positive bacterium in the genus Streptococcus. These bacteria are aerotolerant and an extracellular bacterium, made up of non-motile and non-sporing cocci. It is clinically important for humans. It is an infrequent, but usually pathogenic, part of the skin microbiota. It is the predominant species harboring the Lancefield group A antigen, and is often called group A streptococcus (GAS). However, both Streptococcus dysgalactiae and the Streptococcus anginosus group can possess group A antigen. Group A streptococci when grown on blood agar typically produces small zones of beta-hemolysis, a complete destruction of red blood cells. It is thus also called group A (beta-hemolytic) streptococcus (GABHS), and can make colonies greater than 5 mm in size.
Shigella is a genus of Gram-negative, facultative aerobic, non-spore-forming, nonmotile, rod-shaped bacteria genetically closely related to E. coli. The genus is named after Kiyoshi Shiga, who first discovered it in 1897.
Neisseria is a large genus of bacteria that colonize the mucosal surfaces of many animals. Of the 11 species that colonize humans, only two are pathogens, N. meningitidis and N. gonorrhoeae. Most gonoccocal infections are asymptomatic and self-resolving, and epidemic strains of the meningococcus may be carried in >95% of a population where systemic disease occurs at <1% prevalence.
Listeria monocytogenes is the species of pathogenic bacteria that causes the infection listeriosis. It is a facultative anaerobic bacterium, capable of surviving in the presence or absence of oxygen. It can grow and reproduce inside the host's cells and is one of the most virulent foodborne pathogens, with 20 to 30% of foodborne listeriosis infections in high-risk individuals may be fatal. Responsible for an estimated 1,600 illnesses and 260 deaths in the United States annually, listeriosis ranks third in total number of deaths among foodborne bacterial pathogens, with fatality rates exceeding even Salmonella spp. and Clostridium botulinum. In the European Union, listeriosis follows an upward trend that began in 2008, causing 2,161 confirmed cases and 210 reported deaths in 2014, 16% more than in 2013. Listeriosis mortality rates in the US are also higher in the EU than for other foodborne pathogens.
Legionella pneumophila is a thin, aerobic, pleomorphic, flagellated, non-spore-forming, Gram-negative bacterium of the genus Legionella. L. pneumophila is the primary human pathogenic bacterium in this group and is the causative agent of Legionnaires' disease, also known as legionellosis.
Francisella is a genus of pathogenic, Gram-negative bacteria. They are small coccobacillary or rod-shaped, nonmotile organisms, which are also facultative intracellular parasites of macrophages. Strict aerobes, Francisella colonies bear a morphological resemblance to those of the genus Brucella.
Swine brucellosis is a zoonosis affecting pigs, caused by the bacterium Brucella suis. The disease typically causes chronic inflammatory lesions in the reproductive organs of susceptible animals or orchitis, and may even affect joints and other organs. The most common symptom is abortion in pregnant susceptible sows at any stage of gestation. Other manifestations are temporary or permanent sterility, lameness, posterior paralysis, spondylitis, and abscess formation. It is transmitted mainly by ingestion of infected tissues or fluids, semen during breeding, and suckling infected animals.
Virulence factors are molecules produced by bacteria, viruses, fungi, and protozoa that add to their effectiveness and enable them to achieve the following:
Pasteurella multocida is a Gram-negative, nonmotile, penicillin-sensitive coccobacillus belonging to the Pasteurellaceae family. Strains belonging to the species are currently classified into five serogroups based on capsular composition and 16 somatic serovars (1-16). P. multocida is the cause of a range of diseases in mammals and birds, including fowl cholera in poultry, atrophic rhinitis in pigs, and bovine hemorrhagic septicemia in cattle and buffalo. It can also cause a zoonotic infection in humans, which typically is a result of bites or scratches from domestic pets. Many mammals and birds harbor it as part of their normal respiratory microbiota.
Ralstonia solanacearum is an aerobic non-spore-forming, Gram-negative, plant pathogenic bacterium. R. solanacearum is soil-borne and motile with a polar flagellar tuft. It colonises the xylem, causing bacterial wilt in a very wide range of potential host plants. It is known as Granville wilt when it occurs in tobacco. Bacterial wilts of tomato, pepper, eggplant, and Irish potato caused by R. solanacearum were among the first diseases that Erwin Frink Smith proved to be caused by a bacterial pathogen. Because of its devastating lethality, R. solanacearum is now of the more intensively studied phytopathogenic bacteria and bacterial wilt of tomato is a model system for investigating mechanisms of pathogenesis. Ralstonia was recently classified as Pseudomonas with similarity in most aspects, except that it does not produce fluorescent pigment like Pseudomonas. The genomes from different strains varies from 5.5 Mb up to 6 Mb, roughly being 3.5 Mb of a chromosome and 2 Mb of a megaplasmid. While the strain GMI1000 was one of the first phytopathogenic bacterias to have its genome completed, the strain UY031 was the first R. solanacearum to have its methylome reported. Within the R. solanacearum species complex, the four major monophyletic clusters of strains are termed phylotypes, that are geographically distinct: phylotypes I-IV are found in Asia, America, Africa, and Oceania, respectively.
Listeriolysin O (LLO) is a hemolysin produced by the bacterium Listeria monocytogenes, the pathogen responsible for causing listeriosis. The toxin may be considered a virulence factor, since it is crucial for the virulence of L. monocytogenes.
Rhodococcus equi is a Gram-positive coccobacillus bacterium. The organism is commonly found in dry and dusty soil and can be important for diseases of domesticated animals. The frequency of infection can reach near 60%. R. equi is an important pathogen causing pneumonia in foals. Since 2008, R. equi has been known to infect wild boar and domestic pigs. R. equi can infect humans. At-risk groups are immunocompromised people, such as HIV-AIDS patients or transplant recipients. Rhodococcus infection in these patients resemble clinical and pathological signs of pulmonary tuberculosis. It is facultative intracellular.
Bacillus anthracis is the etiologic agent of anthrax—a common disease of livestock and, occasionally, of humans—and the only obligate pathogen within the genus Bacillus. B. anthracis is a Gram-positive, endospore-forming, rod-shaped bacterium, with a width of 1.0–1.2 µm and a length of 3–5 µm. It can be grown in an ordinary nutrient medium under aerobic or anaerobic conditions.
Francisella novicida is a bacterium of the Francisellaceae family, which consist of Gram-negative pathogenic bacteria. These bacteria vary from small cocci to rod-shaped, and are most known for their intracellular parasitic capabilities. In this family, six species have been identified; however, the species F. novicida is under intense scrutiny. Though some believe it should be classified with its own species designation, others argue it should be reclassified as a subspecies under F. tularensis. If it were to be classified as a subspecies, F. novicida would join the other known subspecies including F. t. tularensis and F. t. holarctica. Biochemical assays for identifying F. tularensis subtypes and strains are not ideal because the results are often non-definitive and subject to variation, therefore these assays should only be considered as supplementary tests for identification of Francisella species and subspecies. Several strains of F. novicida or F. novicida-like bacteria have been described, and these strains may be resolved by PCR-based methods.
Allorhizobium vitis is a plant pathogen that infects grapevines. The species is best known for causing a tumor known as crown gall disease. One of the virulent strains, A. vitis S4, is responsible both for crown gall on grapevines and for inducing a hypersensitive response in other plant species. Grapevines that have been affected by crown gall disease produce fewer grapes than unaffected plants. Though not all strains of A. vitis are tumorigenic, most strains can damage plant hosts.
Several small RNAs have been identified in Francisella tularensis, pathogenic bacterium that causes the disease tularaemia. Very little is known about Francisella's regulatory networks that allow this bacterium to survive in many environments.