2 toxins with ADP-ribosyl transferase

Cholera T

Diptheria T

2 toxins with protease activity 

Botulinum T

Anthrax T (lethal and edema factors)

2 pore forming toxins

Alpha - Diptheria T

beta - Anthrax-T

listeriolysin O

What is the causative agent of diptheria?

corynebacterium diphtheriae

gram +

What is treatment for diptheria?

 Treatment consists of immediate administration of antitoxin and 

antibiotics. 

Antitoxin: Injection of anti-diphtheria toxin antibodies 

developed in horses.

preventive measures against diptheria

vaccine - DPT

inactivated toxin - toxoid (combined with vaccine)

What does the diptheria toxin affect

bacteria colonizing the larynx produce - travels via the blood to other tissues (lethal for most human body cells)

Diptheria toxin path through the cell

1. ABT toxin binds to growth factor precursor

2. Receptor mediated endocytosis = early endosome 

3. pH drop unfolds the toxin - makes T hydrophobic = pore in in membrane

4. A translocates through Ts hole into the cytosol and proteolytic clevage

5. The A fragment then catalyzes the ADP- ribosylation of the ELONGATION FACTOR 2 (EF-2) resulting in the inhibition of protein synthesis and death of the cell.

What is the causative agent of Botulism?

Clostridium botulinum, a spore-forming, rod-shaped Gram-positive anaerobic bacterium. 

What causes symptoms of Botulism?

The disease is due to the exotoxin, a neurotoxin, that blocks 

nerve function. The most toxic protein

What does the Botulium Toxin do?

The toxin blocks the release of the neurotransmitter acetylcholine 

from nerve endings thus arresting their function

What does the Botulinum Toxin affect?

peripheral nerve terminals - does not cross blood brain barrier

various proteins

(blocks release of acetylcholine)

Botulin Toxin - binding/internalization

glycolipids and synaptotagmin

botulin toxin

translocation

Acidification of the endosome. 

Hydrophobic region insertion into 

the vesicular membrane. 

Translocation of A subunit and 

reduction of the disulfide bond. 

Botulin Toxin

Enzymatic activity 

Zinc Metalloproteasesthat 

cleave SNARE proteins (large 

family of proteins that 

mediate fusion of vesicles).

What are some medical uses for Botulin toxin?

• Act therapeutically to specifically inactivate specific nerve populations, and thus achieve a therapeutic goal. 

– Dystoniaand muscle spasms: neurological movement disorder 

– Alleviation of pain : the toxin is used to alter sensory inputs to the central nervous system

to the central nervous system.

Anthrax

bacillus anthracis - gram positive spore forming

vegetative and dormant

Portals of entry for anthrax

Gastrointestinal 

Cutaneous 

inhalational (most deadly)

Bacillus anthracis virulence factors

-Capsular component that limit uptake by phagocyticcells 

-Tripartite toxin: Primary agent of tissue destruction and death.

Life cycle of bacillus anthracis

Entry

Germination 

Outgrowth (cytosol)

Vegetative growth