Bacillus anthracis / Anthrax MCDB 132

What disease does Bacillus anthracis cause?

Anthrax

Is B. anthracis gram - or gram +?

Gram +

Does B. anthracis form chains and spores?

Yes, anthracis forms spores and chains.

What shape is Bacillus anthracis?

rod

What is the reservoir for B. anthracis?

soil

What is the transmission for B. anthracis?

spores from soil or animals/ animal products

How is the transmission of B. anthracis similar to the transmission of tetanus?

They are both infections (from their spores) but not contagious. (no human to human transmission)

What are the general symptoms of inhalation anthrax?

Difficulty breathing, shock

What are the symptoms of cutaneous anthrax?

Black, painless ulcer (eschar)

What is the most common type of anthrax disease?

Cutaneous anthrax (95%) of cases

What is the pathogenesis for cutaneous anthrax? (95% of cases)

Spores enter wound, germinate and replicate, lead to skin lesion with gelatinous edema (fluid, swelling). In rare cases, septicemia (blood poisoning) may occur, leading to sepsis.

What is the pathogenesis for gastrointestinal anthrax? (Rare)

Spores are ingested, they germinate and invade intestinal mucosa. Then they spread to lymphatic system. Gastrointestinal anthrax has a high mortality rate even when Abx are given.

What is the pathogenesis for inhalation anthrax? (Rare)

Spores are inhaled, they germinate within lung macrophages. Bugs grow and kill phagocytes. Bacteria enter bloodstream, large numbers appear in blood. This leads to septic shock, high death rate even with Abx.

What are the four steps of Anthrax (Bacillus anthracis) infection/ attack?

1. Spore entry and germination

2. Antiphagocytic capsule

3. Anthrax toxin: 3-component toxin system

4. System shock and death

What is the technical name of the antiphagocytic capsule of anthrax?

poly-gamma-D-glutamic acid

What is poly-gamma-D-glutamic acid (antiphagocytic capsule of anthrax) resistant to?

It is resistant to complement and phagocytes.

How many subunits does the anthrax toxin have?

10 subunits

How many A (active) subunits does anthrax have?

3 (two of them are Lethal factor and Edema Factor)

How many B (binding) subunits does anthrax have?

7 Protective Antigens

Describe how LF of anthrax toxin (AT) works.

• Protease disrupts macrophage cellular signaling

• Host cell lysis, which releases cytokines and bugs (inflammation to immune system)

• Leads to Septic shock

Describe how EF (edema factor) of AT (anthrax toxin) works.

• adenylate cyclase (ACase) → increases cAMP levels (inappropriate cell function)

• ACase requires calmodulin from host cell to activate (similar to pertussis ACT)

• edema caused by increased membrane permeability, leading to fluid secretion and tissue swelling

When does immune-mediated edema occur/ what causes it?

Immune-mediated edema occurs when white blood cells release chemicals, such as histamine, that cause vessels to leak fluid into surrounding tissues.

Describe how the protective antigen (PA) of AT works.

• PA binds to AT receptors

• forms a pore

• releases EF and LF into cytosol

Describe how systemic shock and death is caused by anthrax virulence factors/ the outcome of anthrax.

• septicemia occurs because of the increase of bugs in blood

• vascular leakage: EF and LF damage endothelial cell

• Death comes from respiratory failure and septic shock (organ failure)

What are the two main treatments for anthrax?

• Ciprofloxacin - abx

• Antitoxin → Abs to PA

What are the two versions of the Anthrax vaccine? (which two organisms)

Livestock and humans

What does the livestock vaccine for anthrax have in it?

Live, non-encapsulated toxigenic strain which injects spores subcutaneously (under the skin).

What is in the human vaccine for anthrax and how often is it given?

• it contains the PA (protective antigen) of AT

• 5 doses w/ yearly booster, given to military and at risk individuals only

Why is releasing Bacillus anthracis spores not a good bioterrorism strategy?

Because the spores are not the infectious agent, the bacteria is. There is no human to human transmission.

In what ways can someone contract B. anthracis?

People can contract anthrax if they:

• Come in contact or work with infected animals or contaminated animal products (including hides)

• Consume food or water contaminated by B. anthracis

• Are exposed to anthrax in a laboratory that handles anthrax

• Are exposed during a bioterrorism attack