Anthrax

1
Anthrax

• Erin McDonell
• December 2, 2004

2
Anthrax Bacillus anthracis

• Large
• Rod-shaped
• Gram-positive
• Catalase-positive
• Gamma hemolytic
• Can be grown anaerobically and aerobically

3
B. anthracis

• Unique bacterium-can form endospores!
• Endospores are highly tolerant of severe
  environmental conditions
• Resist U.V. light
• Temperature extremes
• (hot and cold)
• High pH
• High salinity
• Resist drying
• Resist many disinfectants

4
Hosts

• Natural hosts-herbivores
• Spores survive in the soil. Animals become
  infected after soil consumption along with
  plants.
• Humans
• Infection most common in underdeveloped countries
  where livestock is raised and animal byproducts
  are handled and processed
• Three primary routes of infection 3 major types
  of anthrax
• Cutaneous Anthrax
• Inhalational Anthrax
• Gastrointestinal Anthrax

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Modes of Transmission Cutaneous

• Endospores inoculate the skin usually though some
  sort of abrasion or laceration
• Incubation period for spores 1-12 days
• Symptoms
• On skin
• Small papule develops where
• spore entered
• Vesicle
• Necrotic ulcer with black center
• In the body high fever, edema
• (swelling), toxemia
• If infection reaches the systemic nervous system
  can eventually go into shock and die

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Modes of Transmission Inhalational

• Endospores are inhaled
• Inside the lung phagocytized by alveolar
  macrophages
• Transported to mediastinal lymph nodes
• Inside lymph nodes germinate
• Spores are thought to be activated by germinant
  sensors in the lymph node
• B. anthracis sensor operon (Ger-A like)
  recognizes specific host amino acids and
  nucleoside combinations.
• Once activated vegetative metabolism and
  production of toxins begins.

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Modes of transmission GI

• Rarest form of the disease
• Consumption of infected meat products, other food
  products, or water
• Incubation period 1-7 days
• Symptoms
• Intense abdominal pain, fever
• Nausea, vomiting, bloody diarrhea
• Endospores invade GI mucosa, are transported to
  mediastinal lymph nodes, where germination occurs

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Virulence Factors

• Polysaccharide capsule
• Made of poly-D-glutamate polypeptide
• Non-toxic by itself
• Prevents phagocytosis by host immune system
• Production of capsule dependent on pX02 plasmid
• capA, capB, capC, and a depolymerase encode
  membrane-assocated enzymes responsible for
  synthesis of the capsule

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Virulence Factors

• Extracellular toxin Anthrax toxin
• Type three toxin
• One binding domain Protective Antigen (PA)
• Two active domains Edema Factor (EF), and Lethal
  Factor (LF)
• PA EF edema toxin (ETx)
• PA LF lethal toxin (LTx)

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Intoxification Process

• PA is proteolytically cleaved by furin family
  proteases
• Once activated PA forms a heptamer and
  competively binds to EF and LF
• Complex then internalized into an endosome
• Acidic environment facilitates pore formation
  between the endosome and host cell
• Complex translocated across pore to host cell
  cytoplasm
• Recently hypothesized that translocation occurs
  via receptor interaction of lipid rafts on host
  cell
• Lipid rafts are thought to be cholesterol- and
  glycosphingolipid-enriched microdomains of the
  host cell membrane that initiates signaling
  processes necessary for passage of toxin into
  host cell.

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What do the toxins do?

• EF causes drastic increases in cellular cAMP,
  incapacitating phagocytes and preventing cytokine
  formation
• LT functions as a protease cleaving members of
  the MEK family
• After germination in the lymph nodes, LTx disarms
  many branches of the immune system through MEK
  cleavage
• Cytokine responses, and dendritic cell responses
  prevented
• B and T cells prevented from building up host
  immunity
• Eventually macrophages are destroyed when they
  are no longer needed for bacterial replication
• At this point in the infection there are high
  amounts of vascular leakage which can lead to
  systemic hypoxia and shock

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Treatment

• Anthrax vaccine
• Only one licensed for use in the U.S.
• AVA-Anthrax Vaccine Absorbed
• Made from unencapsulated form of the bacterium
• Contains various cellular components, like PA
• 6 Shots 0, 2, 4 weeks, and 6, 12, 18 months
• Annual booster shots
• Minimal adverse reactions as of yet
• Antibiotics
• Penicillin- some resistance cited in literature
• Usually a combination of penicillin and either
  ciprofloxacin or doxycycline given to ensure
  effectiveness

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Bioterrorism

• September 2001- letters sent to media and
  newspaper companies
• Twenty people contracted either inhalational or
  cutaneous anthrax 5 died of the inhalational
  form
• Why such an effective weapon?
• Easy to get a hold of, grow, and store for long
  periods of time
• Easily transportable (envelopes)
• Causes widespread panic
• WHO- estimated that 50 kg of weapon-grade
  anthrax spores released by an aircraft over an
  urban population of 5 million would result in
  250,000 cases
• of predominantly inhalational anthrax having an
  economic impact of 26.2 billion per 100,000
  people exposed.

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Works Cited

• PICTURES
• http//images.google.com/imgres?imgurlhttp//www.
  rppi.org/images/anthrax.jpgimgrefurlhttp//www.r
  ppi.org/wtc/h170w220sz19tbnidCPfuaqO2vdUJ
  tbnh78tbnw100start16prev/images3Fq3Danth
  rax26hl3Den26lr3D26sa3DG
• http//www.postalworkersonline.com/anthrax.jpg
• http//www.nlm.nih.gov/medlineplus/ency/imagepages
  /19058.htm
• http//www.nlm.nih.gov/medlineplus/ency/imagepages
  /19057.htm
• http//www.surrey.ac.uk/SBMS/ACADEMICS_homepage/mc
  fadden_johnjoe/SBMS215.htm
• http//www.medscape.com/content/2002/00/44/29/4429
  37/art-eid442937.fig3.jpg
• INFORMATION
• Anthrax. U.S Food and Drug Administration.
  lthttp//www.fda.gov/cber/vaccine /anthrax.htmgt.
  28 Nov. 2004.
• Brossier et al. 2001 Toxins of Bacillus
  anthracis. Toxicon 39 (11) 1747-1755.
• Cranmer, H. 2004. CBRNE-Anthrax Infection.
  lthttp//www.emedicine.com/EMERG/ topic864.htmgt.
  28 Nov. 2004.
• Kurzchalia, T. 2003. Anthrax toxins rafts into
  cells. The Journal of Cell Biology 160 (3)
  295-296.
• Little et al. 1999. Molecular pathogenesis of
  Bacillus anthracis infection. Microbes and
  Infection 1( 2) 131-139.
• Liu H, et al. 2004. Formation and composition
  of the Bacillus anthracis endospore. Journal of
  Bacteriology 186164-178.
• Moayeri et al. 2004. The roles of anthrax toxin
  in pathogenesis. Current Opinion in
  Microbiology 7 (1) 19-24.
• Oncu et al. 2003. Anthrax- an overview. Med
  Sci Monit 9 (11) RA276-283.
• Todar, K. 2004. Todars Online Textbook of
  Bacteriology Bacillus anthracis and anthrax.
  27 Sept. 2004. lthttptextbookofbacteriology.net/A
  nthrax.htmlgt.
• Use of Anthrax Vaccine in the United States.
  2000. Centers for Disease Control.
  lthttp//www.cdc.gov/mmwr/preview/mmwrhtml/rr4915al
  .htmgt. 28 Nov. 2004.