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Anthrax host
Herbivores, mostly sheep and cattle
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Anthrax History
- First target of Koch's Postulates by Koch
- First target of vaccination- Pasteur
- Been a recognized disease since ancient times
- Name from greek anthrakas (coal) due to black wound in cutaneous disease
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Bacillus anthrax morphology
- Gram + Large rods
- Forms endospores
- Found in soil
- Vegetative form encapsulated
- Non-motile
- Facultative anaerobe
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Endospores
- Can survive decades in environment
- Core contains dipicolinic acid, DNA and ribosomes
- Cortexis made of peptidoglycan
- Exosporium coat of mostly glycoproteins
- Endospores are metabolically inactive
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Formation of Endospore
- 1. Spore septum isolates replicate DNA in cell
- 2. Cell membrane begins to isolate, septum closes
- 3. Forespore forms with two layers
- 4. Peptidoglycan layer forms between cell membrane and spore septum
- 5. Spore coat formed
- 6. Spore released
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Component/purpose of Anthrax capsule/S-layer
- Capsule: polymer of D-glutamic acid (not carb)
- -Anti-phagocytic
- S-layer: paracrystalline layer of protein.
- -unknown, maybe evade complement, create periplasmic-like space, filter macromolecules
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Diseases associated with Anthrax
- Cutaneous anthrax
- Gastrointestinal anthrax
- Inhalation anthrax (bioweapon)
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Cutaneous Anthrax
- Woolsorter's disease
- Endospores enter through abrasion/bite
- 3-5 days after infection, papule forms
- Progresses to necrotic lesion
- Black eschar surrounded by vesicles/edema
- Occupational Hazard
- -Contracted from wool/hide/animal related
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Cutaneous Anthrax Treatment
- Easily treated with antibiotics
- Most common infection
- Can become bloodborne/systemic
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Gastrointestinal Anthrax
- Not in US
- From contaminated meat
- Ulceration of GI tract
- 100% lethal if untreated
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Inhaled Anthrax
- Inhalation of endospores into alvelolar space
- Spreads to mediastinal lymph nodes, then to body
- Almost always fatal
- Contaminated soil/animal
- Bioweapon
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Inhaled Anthrax Pathogenesis
- Spores taken by macrophages to lymph nodes
- Spores germinate in macrophages
- Bacteria escape and infect blood
- -Use edema toxin EdTx and lethal toxin LeTx
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Anthrax virulence factors
- pXO2 plasmid encodes for capsule gene
- pXO1 plasmid encodes for two exotoxins
- These plasmids separate anthrax from other B. cereus
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Anthrax Capsule as Virulence Factor
- Made of poly-y-glutamic acid
- Made up of D-amino acid monomers
- Is weakly immunogenic
- Genes found in pXO2
- Strains cured of pXO2 are slightly attenuated
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AB Toxins as a Virulence toxin
- Both toxins consist of protective antigen+other factor
- Neither component is toxic alone
- Edema toxin:
- -Alters water homeostasis, resulting in edema (massive influx of fluid to area, inhibiting neutrophil action)
- Zinc Protease:
- -Lethal toxin, cleaves proteins, causes macrophages to release proinflammatory cytokines TNF-alpha and IL-1beta
- -Toxin shock
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Edema Factor (EF)
- Encoded by cya gene on pXO1
- Calmodulin-dependent adenylate cyclase (like pertussis)
- Non-lethal, causes edema
- Inhibits phagocytosis by immune cells
- -Impairs oxidative burst of neutrophils
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Lethal Factor (LF)
- Encoded by lef gene on PXO1
- Zinc metalloprotease
- Cleaves MAP kinase kinase
- -impairs intracellular signalling
- Only kills macrophages, unknown mechanism
- Mode of action:
- -Production of ROS
- -Production of IL-1, TNF-alpha
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Protective Antigen (PA)
- encoded by pagA genes on pXO1
- Heptameric four-domain protein
- Host-mediated proteolysis follows receptor binding:
- -Removes amino acids, exposes binding site for EF/LF
- -Exposed site then binds
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Anthrax and Biowarfare
- WWI: German agents infected neutral country livestock being sent to allies
- Late 1930's: Japanese Imperial Army deploys anthrax in Manchuria
- WWII: Canada/UK/US develop anthrax bomb
- 1972: Biological Weapons Convention bans all things related to bioweapons
- 1979: Accidental release of spores from bioweapon plant kills 75 Russians
- 1988: Soviets transport 100 tons of anthrax spores to an island. 11 years later, still good
- 1998: Iraq admits to have produced 2000 liters of spores in gulf war
- US/Russia+13 other countries believed to have anthrax
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Sverdlovsk Incident
- 1979: 120-400+ ill, '75' dead.
- Soviets initially reported it to be contaminated meat, hemorrhagic mediastinitis found
- Disease linked to aerosol leak from weapons plant.
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Anthrax in 9/11
- Beginning Sept. 18th anthrax was mailed to US news media/congressmen FBI concluded it was Dr. Bruce Irvins, scientist at USAMRID
- 22 infected (5 dead), victims where mail-handlers
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Anthrax Vaccine
US uses PA from culture filtrate of an avirulent, nonencapsulated form.
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Surface Proteins of Gram + bacterias
- LPXTG protein
- Hydrophobic tail protein
- GW protein
- Lipoprotein
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Sortase
- Transamidase
- Covalently attaches proteins with LPxTG motif to cell wall
- This is how pilus are assembled in anthrax
- Also attaches some iron acquisition proteins (Hal)
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Important Factoids
- Anthrax forms endospores
- Cause 3 types of diseases
- AB (lethal and edema toxins)
- Anthrax is bioweapon since WWI
- Gram positive bacteria use sortases to attach proteins
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