AssessmentsFrancisella tularensis (Tularemia)
Francisella tularensis (Tularemia)
Contributors:Alexandru Duhaniuc, MD
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.
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.
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.
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 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.
From the bloodstream, it can spread to other organs like the lymph nodes, causing inflammation and suppuration, or pus formation.
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.