Francisella tularensis

Taxobox
color = lightgrey
name = "Francisella tularensis"

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image_width = 240px
image_caption = "F. tularensis" colonies on an agar plate.
regnum = Bacteria
phylum = Proteobacteria
classis = Gamma Proteobacteria
ordo = Thiotrichales
familia = Francisellaceae
genus = "Francisella"
species = "F. tularensis"
binomial = "Francisella tularensis"
binomial_authority = (McCoy and Chapin 1912)
Dorofe'ev 1947

"Francisella tularensis" is a pathogenic species of gram-negative bacteria and the causative agent of tularemia or rabbit fever.cite book | author = Ryan KJ; Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th ed. | pages = pp. 488–90 | publisher = McGraw Hill | year = 2004 | id = ISBN 0-8385-8529-9 ] Due to its ease of spread by aerosol and its high virulence, "F. tularensis" is classified as a Class A agent by the U.S. government.cite journal | author = Oyston P, Sjostedt A, Titball R | title = Tularaemia: bioterrorism defence renews interest in "Francisella tularensis" | journal = Nat Rev Microbiol | volume = 2 | issue = 12 | pages = 967–78 | year = 2004 | pmid = 15550942 | doi = 10.1038/nrmicro1045]

Subspecies

Four subspecies (biovars) of "F. tularensis" have been classified. The biovar "tularensis" (or type A) is found predominantly in North America and is the most virulent of the four known subspecies and is associated with lethal pulmomary infections. Biovar "palearctica" (also known as biovar "holarctica" or type B) is found predominantly in Europe and Asia but rarely leads to fatal disease. An attenuated live vaccine strain of subspecies "palearctica" has been described, though it is not yet fully licensed by the FDA as a vaccine. Subspecies "novicida" was characterized as a relatively nonvirulent strain; only two tularemia cases in North America have been attributed to "novicida" and these were only in severely immunocompromised individuals. The fourth, biovar "mediasiatica", is found primarily in central Asia; little is currently known about this subspecies or its ability to infect humans.

Pathogenesis

"F. tularensis" is capable of infecting a number of small mammals such as voles, rabbits, and muskrats, as well as 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.

Infection with "F. tularensis" can occur via several routes. The most common occurs via skin contact, yielding an "ulceroglandular" form of the disease. Inhalation of bacteria - particularly biovar "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 brushcutting 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".

Life Cycle

"F. tularensis" is a facultative intracellular bacterium that is capable of infecting most cell types but primarily infects macrophages in the host organism. "F. tularensis" entry into the macrophage occurs via 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.

Virulence Factors

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 facilitate degradation of the phagosome. Specifically, a hemolysin protein NlyA with similarity to "Pseudomonas aeruginosa" HlyA was characterized in biovar "novicida" whereas an acid phospholipase C AcpA has been found in other strains to act as a hemolysin.

While "F. tularensis" does not contain virulence secretion systems typical of some better-characterized pathogenic bacteria, it does contain a number of ATP binding cassette (ABC) proteins that may be linked to the secretion of virulence factors.cite journal | author = Atkins H, Dassa E, Walker N, Griffin K, Harland D, Taylor R, Duffield M, Titball R | title = The identification and evaluation of ATP binding cassette systems in the intracellular bacterium "Francisella tularensis" | journal = Res Microbiol | volume = 157 | issue = 6 | pages = 593–604 | year = 2006| pmid = 16503121 | doi = 10.1016/j.resmic.2005.12.004] In addition, "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" 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 that 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 it is not clear what the contributions of IglC and other genes are.

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 will divide into two daughter cells, each of which contains identical genetic information. Genetic variation may be introduced via mutation or horizontal gene transfer.

The genome of "F. tularensis" biovar tularensis strain SCHU4 has been sequenced.cite journal | author = Larsson P, Oyston P, Chain P, "et al". | title = The complete genome sequence of "Francisella tularensis", the causative agent of tularemia | journal = Nat Genet | volume = 37 | issue = 2 | pages = 153–9 | year = 2005 | pmid = 15640799 | doi = 10.1038/ng1499] The studies resulting from the sequencing suggest that a number of gene coding regions in the "F. tularensis" genome are disrupted by mutations and thus create blocks in a number of metabolic and synthetic pathways that are required for survival. This indicates that "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.

Genomics

* [http://www.genomesonline.org/search.cgi?colcol=all&goldstamp=ALL&gen_type=ALL&org_name1=genus&gensp=Francisella&org_domain=ALL&org_status=ALL&size2=ALL&org_size=Kb&gen_gc=ALL&phylogeny2=ALL&gen_institution=ALL&gen_funding=ALL&gen_data=ALL&cont=ALL&gen_country=ALL&gen_pheno=ALL&gen_eco=ALL&gen_disease=ALL&gen_relevance=ALL&gen_avail=ALL&selection=submit+search Francisella Genome Projects] (from [http://www.genomesonline.org Genomes OnLine Database] )
* [http://img.jgi.doe.gov/cgi-bin/pub/main.cgi?section=TaxonList&page=lineageMicrobes&genus=Francisella Comparative Analysis of Francisella Genomes] (at DOE's IMG system)

References

External links

* [http://www.cdc.gov/ncidod/diseases/submenus/sub_tularemia.htm "Francisella tularensis" information] from the CDC/National Center for Infectious Diesase:
* [http://www.biohealthbase.org/GSearch/statsAutomation.do?decorator=Francisella BioHealthBase Bioinformatics Resource Center] The National Institute of Allergy and Infectious Disease (NIAID) supports a public database describing the molecular genetics of "F. tularensis". The website describes the genes, proteins, and cellular characteristics of the pathogen.