Lectures 24 & 25 - Bacterial Toxins

Toxicity

Ability of an organism to cause disease through a preformed toxin that inhibits host cell function/kills host cell

Invasiveness

Ability of an organism to grow in host tissue in such large numbers that the pathogen inhibits host function.

Toxin Type: Class I

Bind target on cell surface not translocated into the cell (superantigens)

Toxin Type: Class II

Host cell membrane disrupting toxins. Commonly secreted by T1S pathways.

Toxin Type: Class III

Single gene produces A and B components that are covalently attached by disulfide bond. They are encoded by a single gene but are subsequently cleaved. (Diphtheria and botulinum toxins)
Complex compound AB toxin composed of several A and b components.
B component binds and the A component is the active component. These are commonly secreted by T2S pathways, Cholera toxin.

Class III modes of action: Diphtheria toxin

The toxin receptor is HB-EGF. The receptor is found on many types of cells. Translocated through pH dependent process after endocytosis. Diphtheria toxin is potent enough that a single molecule can kill a cell. It can stop protein synthesis in a cell if it is exposed.

Class III modes of actionI: Cholera Toxin

Enterotoxin. ADP-ribosylase that targets the intestine. ADP ribosylates an arginine residue on a G protein that controls cyclic AMP levels in the host cell. The cell will lose control of ion flow and results in massive water loss. 50-100 Liters of water lost as diarrhea.

Shiga Toxin

Enterotoxin. Ribonuclease (targets rRNA). This toxin cleaves host cell rRNA which results in the shutdown of protein synthesis.

Read botulism and tetanus C12: pg247-251

Botulinum toxins

Target peripheral neurons and cause flaccid paralysis

Tetanus toxins

Target CNS neurons and cause spastic paralysis

Class II mode of action: Listeriolysin O L. monocytogenes, Streptolysin O from S. pyogenes, and Alpha toxin from Staphylococcus aureus

Pore forming toxin bind to membrane and polymerize. Toxin inserts into membrane, creates channel, and the cell swells/lyses.

Class II mode of action: Phospholipase C and D

Cleaves phosphate groups in membrane and it becomes unstable

Class I mode of action: Streptococcus and Staphylococcus

Mostly associated with GSP pathway. Superantigen engages Class II MHC The TH cell response is now nonspecific and causes toxic shock syndrome.
This process is independent of antigens. The abnormally high stimulation of T cells causes Massive release of cytokine IL-2 which leads to nausea, vomiting, fever, and may lead to death.