Francisella tularensis (Tularemia)
Definitions & Key takeaways
Francisella tularensis is a gram-negative, facultative intracellular coccobacillus, known to cause a zoonotic infection known as tularemia. Tularemia can be transmitted to humans by ticks, deer flies, rabbits, and deer flies.
Depending on the transmission route, tularemia has several forms, including ulceroglandular, oculoglandular, and pneumonic. The ulceroglandular form occurs when the bacteria enter through a break in the skin. The ulcer at the site of infection becomes swollen and painful, and may discharge pus. Glands near the ulcer may also become enlarged. Next, the oculoglandular form occurs when the bacteria are spread to the eyes. Symptoms include redness, swelling, and pain in the eyes, photophobia, as well as swollen lymph nodes., Finally, the pneumonic form occurs when the bacteria are inhaled and resulting in pneumonia. Symptoms include fever, chest pain, and coughing up blood.
Francisella tularensis is a Gram-negative coccobacillus, which means that shape-wise, it’s somewhere between a spherical coccus and a rod-like bacillus.
In humans, it causes a zoonotic infection called tularemia, also called rabbit fever. This bacteria is also considered a category A bioterrorism agent which means it is of highest concern for bioterrorism use, because of its low infectious dose and high associated mortality.
Now, Francisella tularensis has a thin peptidoglycan layer, so it doesn’t retain the crystal violet dye during Gram staining.
Instead, like any other Gram-negative bacteria, it stains pink with safranin dye. Alright, now Francisella tularensis is non-motile, non-spore forming, facultative intracellular which means it can survive both outside and inside the cell and aerobic which means it can survive only in the presence of oxygen.
Also, it’s oxidase and urease negative which means it doesn’t produce these enzymes. Finally, Francisella tularensis is a fastidious bacteria which requires enriched medium for growth.
And Francisella tularensis really loves cysteine, so it only grows in about 47 to 72 hours on cysteine-enriched mediums like cysteine enriched chocolate agar, BCYE and CHAB.
Cysteine enriched chocolate agar, named so for its color, actually contains cysteine and lysed red blood cells - so no chocolate products were harmed in the making of this medium.
BCYE stands for buffered charcoal yeast extract, so it contains activated charcoal, yeast extract, and L-cysteine. On these two mediums, Francisella tularensis forms round, grey-white colonies.
Now, Francisella tularensis has a number of virulence factors, that are like assault weaponry that help it attack and destroy the host cells, and evade the immune system.
So first, Francisella tularensis is encapsulated, meaning it’s covered by a polysaccharide layer called a capsule. And right underneath that capsule, there’s also an outer membrane, which consists of lipopolysaccharide - or LPS for short.
The most interesting part is that normally, the LPS of Gram-negative bacteria binds to a protein found on immune cells like macrophages, called Toll-like receptor 4, or TLR4 for short, which is involved in the activation of innate immune system.
And this leads to the production of pro-inflammatory cytokines and nitric oxide that neutralize the invader. However, the LPS of Francisella tularensis is inactive which means that TLR4 does not bind to it, so the innate immune system does not get activated - so it’s kinda like a thief breaking into a house without triggering the alarm.
So next, Francisella tularensis uses its type IV pili, which are hair-like extensions found on its capsule, to attach to macrophages.
Once attached to macrophages, the bacteria is ingested, and it gets wrapped up in a vesicle called a phagosome. Normally, the phagosome would merge with the lysosome, to form a phagolysosome and subject the invader to oxidative burst - which is when damaging free radicals are released inside the phagolysosome.
However, Francisella tularensis produce an acid phosphatase, called AcpA, which inhibits the fusion between phagosome and lysosome, helping it avoid intracellular destruction.
And now, Francisella tularensis can replicate safely inside the macrophage. And to replicate, it needs iron, so it also produces a siderophore, which is a term used for a group of small, high-affinity, iron chelating compounds that snatch iron from host cells.
Eventually, after Francisella tularensis has replicated enough, the macrophage bursts and releases the bacteria into the bloodstream, causing sepsis.
From the bloodstream, it can spread to other organs like the lymph nodes, causing inflammation and suppuration, or pus formation.
Alternatively, it can spread to the liver, causing hepatitis, the kidneys, causing renal failure, or the lungs, causing pneumonia.
Now, Francisella tularensis is transmitted through ticks, rabbits and deer flies, and the infection can be acquired several ways.
Depending on the route of transmission, tularemia has six forms - ulceroglandular, glandular, oculoglandular, oropharyngeal, pneumonic and typhoidal.
So, the ulceroglandular and the glandular forms are transmitted through insect bites such as ticks and flies. This leads to an infection of the skin and lymph nodes with the ulceroglandular form, or just the lymph nodes with the glandular form.
The oculoglandular form occurs when bacteria gain access to the conjunctiva, which can happen by splashing infected material into the eyes or rubbing the eyes with contaminated fingers.
The oropharyngeal form is transmitted by ingestion of contaminated food or water, and it affects the mouth and the throat.
The pneumonic form presents as pneumonia, and it can be primary, when the disease results from direct inhalation of the bacteria into the lungs.
Alternatively, the pneumonic form can be secondary, which results from a hematogenous spread to the lung. Finally, the typhoidal form may result from any portal of entry and it can lead to a systemic febrile illness.
Now, symptoms develop after an incubation period of 3 to 6 days, and all forms associate nonspecific symptoms such as fever, chills, malaise, anorexia and chest or muscle soreness.
Specific symptoms depend on the form of disease. With the ulceroglandular form, there’s lymphadenopathy, meaning enlarged lymph nodes, which may be painful to touch, and there’s a single red, raised lesion with a crater at its center at the site of the bite.
With the glandular form, there’s just painful lymphadenopathy. With the oculoglandular form, there’s eye pain, increased tearing, photophobia, which is eye pain due to light exposure, periorbital edema, which is swelling around the eyes, periorbital erythema, which is redness around the eyes and regional adenopathy.
With the oropharyngeal form, symptoms include a sore throat, difficulty swallowing, and cervical lymphadenopathy. The pneumonic form associates a dry cough, breathing difficulties and chest pain.
And finally, the typhoidal form ranges from acute sepsis to chronic febrile illness and develops with high fever, chills, weight loss, headache, myalgias, abdominal pain, diarrhea, vomiting and diffuse abdominal tenderness.
Diagnosis is based on serologic tests, like latex agglutination or ELISA, which show an increase in both IgM and IgG after 2 weeks of infection.
Finally, there are some fast tests to detect Francisella tularensis, such as PCR and direct fluorescent antibody test, or DFA for short, but these are not yet available for routine testing.
Treatment is done with antibiotics like aminoglycosides, particularly streptomycin and gentamicin. Alternatives include tetracyclines, fluoroquinolones and chloramphenicol.
Alright, as a quick recap, Francisella tularensis is a Gram-negative coccobacillus, that produces a zoonotic disease called tularemia, transmitted by ticks, rabbits and deer flies.
It is non-motile, non-spore forming, facultative intracellular, aerobic, oxidase and urease negative. It grows on cysteine-enriched mediums like cysteine enriched chocolate agar, BCYE and CHAB.
Its virulence factors include the capsule with type IV pili, and LPS, which help it invade host cells, as well as acid phosphatase AcpA that helps it avoid intracellular destruction, and a siderophore that snatches iron from host cells.
Tularemia has six different forms - ulceroglandular, glandular, oculoglandular, oropharyngeal, pneumonic and typhoidal. It can be diagnosed with serological tests such as latex agglutination and ELISA and also, with cultures from blood, lymph node drainage, skin lesion drainage or sputum.
Treatment is usually done with with streptomycin and gentamicin.
No notes for this video yet
Try adding a note below