Anthrax: Bacillus anthracis characteristics

• Bacillus spp are spore-forming Gram-positive rods

Medically Important Bacillus Species

• Two medically important Bacillus species are Bacillus anthracis and Bacillus cereus
• Bacillus anthracis causes Anthrax
• Bacillus cereus causes food poisioning

Bacillus anthracis

• B. anthracis is a large Gram-positive rod with square ends, frequently found in chains
• B. anthracis is non-motile
• B. anthracis has a unique antiphagocytic capsule composed of d-glutamate
• Other bacteria have polysaccharide capsules
• Anthrax toxin is encoded on one plasma
• Polyglutamate capsule is encoded on a different plasmid

Anthrax Disease Spectrum

• Anthrax is common in animals, but rare in humans
• Human disease occurs in three main forms: cutaneous, pulmonary, and gastrointestinal
• In 2001, an outbreak of inhalation and cutaneous anthrax occurred in the US
• The outbreak was caused by sending spores of the organism through the mail
• There were 18 cases and 5 deaths

Anthrax Transmission

• Spores of B. anthracis persist in soil for years
• Humans are most often infected cutaneously at the time of trauma to skin
• Spores are allowed to enter through animal products
• Spores can also be inhaled into the respiratory tract
• Pulmonary (inhalation) anthrax occurs when spores are inhaled into the lungs
• Inhalation anthrax is not communicable from person to person

Pulmonary Anthrax

• After being inhaled into the lung, the organism moves rapidly to the mediastinal lymph nodes, this causes hemorrhagic mediastrinitis
• It is not transmitted by respiratory route

Gastrointestinal Anthrax

• Occurs when contaminated meat is ingested

Anthrax Pathogenesis

• Pathogenesis is primarily based on the production of two exotoxins (collectively known as Anthrax Toxin)
• The two exotoxins, Edema Factor and Lethal Factor, each consist of two proteins in an A-B subunit configuration
• The B (Binding) subunit in each of the two exotoxins is Protective Antigen
• The A (Active subunit) has enzymatic activity
• The name Protective Antigen refers to the fact that an antibody against this protein protects against disease

Anthrax Exotoxins

• Exotoxin Edema Factor is an adenylate cyclase that causes an increase in intracellular concentration of cyclic adenosine monophosphate [AMP]
• This causes an outpouring of fluid from the cell into the extracellular space manifestating as edema similar to cholera toxin action
• Exotoxin Lethal Factor is a protease that cleaves phosphokinase, this activates mitogen-activated protein kinase (MAPK) signal transduction pathway, controlling human cell growth
• Cleavage of phosphokinase inhibits cell growth
• Protective Antigen forms pores in the human cell membrane that allows Edema Factor and Lethal Factor to enter the cell

Cutaneous Anthrax

• Typical lesion of cutaneous anthrax is a painless ulcer with black eschar (crust, scab)
• Local edema is striking
• The lesion is called a "Malignant Pustule"
• Untreated cases progress to bacteremia and death

Pulmonary Anthrax

• Often described as "Woolsorter's Disease”
• Begins with nonspecific respiratory tract resembling influenza, specifically a dry cough and substernal pressure
• Rapidly progresses to Hemorrhagic Mediastinitis, Bloody Pleural Effusions, Septic Shock, and Death
• Lungs are infected, but the classic features and X-ray picture of pneumonia are not present
• Mediastinal widening seen on chest X-ray is an important diagnostic criterion
• Hemorrhagic Mediastinitis and Hemorrhagic Meningitis are severe and life-threatening complications

Gastrointestinal Anthrax

• Symptoms: vomiting, abdominal pain, and bloody diarrhea

Lab Diagnosis for Anthrax

• Smears show large, Gram-positive rods in chains
• Spores are usually not seen in smears of Exudate because spores form only when nutrients are insufficient, while nutrients are plentiful in infected tissue
• Non-hemolytic colonies form on Blood agar aerobically
• In case of a bioterror attack, rapid diagnosis can be performed in special laboratories using PCR-based assays
• Another rapid diagnostic procedure is the Direct Fluorescent Antibody test that detects antigens of the organism in the lesion
• Serologic tests, such as an ELISA test for antibodies, require acute and convalescent serum samples and can only be used to make a diagnosis retrospectively

Treatment for Anthrax

• Ciprofloxacin is the drug of choice
• Doxycycline is an alternative drug
• No resistant strains have been identified

Prevention of Anthrax

• Ciprofloxacin or Doxycycline was used as prophylaxis in those exposed during the 2001 outbreak in the United States
• People at high risk can be immunized with a cell-free vaccine containing purified protective antigen as an immunogen
• The vaccine is weakly immunogenic, six doses of vaccine over an 18-month period are given, along with annual boosters to maintain protection
• Animals that die of anthrax should be incinerated, rather than buried, to prevent the soil from becoming contaminated with spores

Bacillus cereus and Food Poisoning

• Bacillus cereus causes food poisoning
• Spores on grains such as rice survive steaming and rapid frying
• Spores germinate when rice is kept warm for many hours
• The portal of entry is the gastrointestinal tract
• Bacillus cereus produces two enterotoxins

Bacillus cereus' Mode of Action

• Mode of action of one of the enterotoxins is similar to that of cholera toxin and adds adenosine diphosphate ribose [ADP-ribosylation] to a G protein, which stimulates adenylate cyclase
• This leads to an increased concentration of cyclic AMP within the enterocyte
• Mode of action of the other enterotoxin resembles that of staphylococcal enterotoxin as a superantigen
• Superantigens are potent, as they can cause fever, shock, death, inflammation, cytotoxicity, T-cell deletion, and autoimmunity
• Superantigens are predominantly bacterial in origin, including staphylococcal enterotoxin and toxin-1, which are responsible for toxic shock syndrome

Bacillus cereus Clinical Findings

• Two syndromes include one with a short incubation period (4 hours) consisting primarily of nausea and vomiting, similar to staphylococcal food poisoning
• The other has a long incubation period (18 hours) and features watery, non-bloody diarrhea, resembling clostridial gastroenteritis

Bacillus cereus Lab Diagnosis

• Lab diagnosis is not usually done

Bacillus cereus Treatment

• Only symptomatic treatment is given

Bacillus cereus Prevention

• There is no specific means of prevention
• Rice should not be kept warm for long periods

Test your knowledge of Bacillus anthracis, its unique characteristics, transmission, and forms of anthrax. Learn about symptoms, diagnosis, and why it poses a threat to human health. This quiz covers cutaneous and inhalational presentations.