Francisella tularensis: Properties, Pathogenesis, Lab Diagnosis

Francisella tularensis causes life-threatening infections in animals (rabbits, hares, and rodents) and people (zoonotic disease). It is also known as ‘Rabbit Fever’ or ‘Deer Fly fever.’

Francisella tularensis basic feature

Properties of Francisella tularensis

  • Causes highly infectious (as few as 10 organisms can cause disease and the organism can enter the human body through skin, eyes, mouth, or lungs) but treatable (can be treated successfully with antibiotics).
  • Agent of bioterrorism: Because of its highly infectious nature F. tularensis is currently classified as a category A agent of bioterrorism.
  • Bacterial culture of tularemia should be carried out in a biosafety level 3 (BSL3) laboratory.
  • Gram-negative coccobacillus
  • Non-motile
  • Non-spore forming
  • Facultative intracellular bacteria
  • Aerobic
  • Fastidious bacteria (requires cysteine enriched medium for growth)—Cysteine enriched chocolate agar, BCYE agar, and CHAB agar (cysteine heart agar with blood).
Francisella tularensis identification flowchart
Image source: Laboratory Response Network (LRN)


Mode of Transmission

Source: It persists in contaminated environments, insects, and animal carries.

Transmission routes:

  • Bite of blood-sucking insects such as tick and deer fly
  • Skin contact with infected animals
  • Ingestion of contaminated water
  • Inhalation of contaminated aerosols or agricultural and landscaping dust
  • Laboratory exposure: In the cases of unanticipated events, laboratory workers may get exposed and acquire infection with F. tularensis while subculturing positive broth blood cultures, performing Gram’s staining, or examining agar plates


F. tularensis has four subspecies: tularensis, holarctica, novicida, and mediasiatica. The first three species are found in North America whereas subspecies mediasiatica is found in central Asia. Subspecies tularensis is the most common and the most virulent among all. It has been isolated only from North America, which accounts for more than 70% of cases.

Increasing number of cases due to other subspecies have been reported from the Scandinavian countries, Eastern Europe and Siberia.

Virulence Factors

Once F. tularensis is engulfed by immune cells (macrophages) that routinely kill bacteria, it replicates and evades parts of the immune system using an array of virulence factors:

  • Capsule (anti-phagocytic in nature)
  • The outer membrane (LPS layer) helps to thwart innate immune response as it evades recognition by Toll-Like receptors (TLR)
  • Type IV Pili (adherence)
  • Acid phosphatase: Prevents the fusion of phagosome with the lysosome.
  • Siderophores: acquisition of iron

Clinical Manifestations  

Tularemia symptoms usually appear within 3-5 days of infection, but may also appear up to 15 days later. Tularemia is characterized by various clinical syndromes depending on how the person was infected.
Main forms of the disease are:

Ulceroglandular tularemia

It is the most common form, (75-85% of total cases), characterized by an ulcerative lesion at  the site of inoculation, with regional lymphadenopathy (armpit or groin.)

Glandular tularemia

It presents with swollen lymph nodes (without ulcer)

Pulmonary tularemia

  • It can result from aerosol inhalation (laboratory workers) or can spread to the lungs following bacteremia if other forms of tularemia are left untreated.
  • Symptoms include cough, chest pain, and difficulty breathing.
  • Most serious forms of tularemia

Oropharyngeal tularemia

It occurs following the ingestion of contaminated undercooked meat. It is characterized by membranous pharyngitis with cervical lymphadenopathy.

Oculoglandular tularemia

This form occurs when the bacteria enter through the eye. It is characterized by purulent conjunctivitis with preauricular lymphadenopathy.

Typhoid-like illness

It presents with the standard, nonspecific febrile (fever) symptoms, but without a known route of infection (via the skin, eye, ingestion, or inhalation)

Laboratory Diagnosis

Difficult to diagnose because it’s a rare disease with nonspecific signs and symptoms. Diagnosis may rely on epidemiologic evidence (e.g., history of mowing the lawn in an endemic area)


Ulcer scrapings, lymph node biopsy, gastric washings, sputum, and blood.


Isolation is very difficult as F. tularensis is highly fastidious

It needs special media such as:

  • BCG agar (blood cysteine glucose agar)
  • CHAB agar (cysteine heart agar supplemented with 9% heated sheep blood).
F. tularensis in cysteine enriched chocolate agar

Specimens are inoculated onto the media and incubated at 37oC for 2-4 days aerobically as F. tularensis is an obligate aerobe.

Colonies are blue-gray, round, smooth, and slightly mucoid with small zone of alpha-hemolysis.

Safety precautions such as biosafety level III must be used to handle clinical specimens to avoid the risk of laboratory-acquired infections.


  • F. turalensis is a small gram-negative coccobacillus with bipolar appearance, non-motile and capsulated.
  • It is weakly catalase positive, oxidase negative and H2S positive
  • It produces acid but no gas from glucose, maltose and mannose.
  • Direct fluorescent antibody tests can be done with commercially available antisera, directly from the culture colonies for subsequent identification.

Antibody detection

It is the mainstay of diagnosis as isolation is difficult. Agglutination test (latex and tube agglutination) and ELISA formats are available .

Molecular Diagnosis

PCR assay has been used to detect F. tularensis specific genes encoding the outer-membrane proteins. It can also differentiate subspecies.

Prevention & Treatment

Steps to prevent tularemia include:

  • Using insect repellent
  • Wearing gloves when handling sick or dead animals
  • Avoiding mowing over dead animals

Streptomycin, gentamicin, doxycycline, and ciprofloxacin are used to treat tularemia. Treatment usually lasts 10 to 21 days depending on the stage of illness and the medication used.


  1. Madigan Michael T, Bender, Kelly S, Buckley, Daniel H, Sattley, W. Matthew, & Stahl, David A. (2018). Brock Biology of Microorganisms (15th Edition). Pearson.
  2. Color Atlas and Textbook of Diagnostic Microbiology, Koneman, 5th edition

Acharya Tankeshwar

Hello, thank you for visiting my blog. I am Tankeshwar Acharya. Blogging is my passion. As an asst. professor, I am teaching microbiology and immunology to medical and nursing students at PAHS, Nepal. I have been working as a microbiologist at Patan hospital for more than 10 years.

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