ADVERTISEMENTS:
Based on activity, toxins are divided into three types: type I (that act the cell membrane), type II (that attack the cell membrane), and type III (that penetrate the membrane to act inside the cell).
1. Membrane Transducing Toxins:
These type of toxins are type I toxins which damage host cells by subtle means through inappropriate activation of cellular receptors. They send wrong message into the cell which confuses the normal routes of communication.
The examples are: the stable toxin (ST) of E. coli and emetic toxin of B. cereus. The ST binds to membrane receptors to stimulate guanyl cyclase and give rise to the intracellular message (cGMP). The cGMP activates protein kinase G and modulates several signalling pathways.
ADVERTISEMENTS:
Bacterial superantigenic toxins directly stimulate immune response by acting as mitogens. They bind to the T cell receptor and MHC Class II antigen directly and activate one or several susets of about 5-20% of T cells.
Examples of superantigens are enterotoxins (causing food poisoning) and exotoxins (causing toxic sock) of S. aureus, and erythrogenic toxins of S. pyogenes.
2. Membrane-Damaging Toxins:
This group of toxins is called type II toxins which directly act on cell membrane, form holes resulting in cell death.
More than 100 toxins have been identified and categorised into several groups as given below:
i. Pore Forming Toxins:
Such toxins enter into the cell membrane as oligomers and form pores. The size of pores differ with different toxins. Some pore forming toxins have cellular activity i.e. invoke cytokine production. Be- sides, many intracellular toxins induce pores due to translocation of their catalytic domains across the membrane into cytosol.
The thio activated cholesterol-bing toxins are produced by four genera of Gram-positive bacteria, for example species of Streptococcus (e.g. streptolysin O, pneumolysin).
Listeria (listerolysin O, ivanolysin), Clostridium (tetanolysin, perfringolysin O, septicolysin O, histolyticolysin O, chauveolysin), and Bacillus (cereolysin O, alveolysin, thuringolysin O). These toxins attack cells containing cholesterol in their membrane and form pores of about 30-40 nm having 30 monomers.
Gram-negative bacteria produce RTX toxins, for example E. coli, haemolysin, leukotoxins from Pasteurella haemolytica, Proteus, Bordetella adenylate cyclase. These toxins form pores of about 1-2 nm consisting of 7 monomers and damage the normal function of host cells. The a-toxin of S. aureus form pores in host cell which results in cell death through apoptosis.
ii. Toxins that Damage Membrane Enzymatically:
There are many toxins that damage host’s cell membrane enzymatically. For example phospholipases produced by L. monocytogenes, S. aureus, P. aeruginosa, B. cereus, and Aeromonas. Phospholipase C (PLC) or a-toxin of C. perfringens has necrotic and cytolytic activity. PLC of P. aeruginosa damages lung surfactant in human. Proteases produced by Porphyromonas gingivalis is implicated in gum disease.
3. Intracellular Toxins:
These are type III toxins which act in most subtle way. They act in different stages (Fig. 27.22). They have to gain intracellular access, survive attack by proteases and protons and trick the cell into them to their target and destroy enzymatically. They are the most deadly group of toxins, for example botulinum and tetanus neurotoxins are lethal to human at a dose of about 0.1 ng and affect nerves.
Neurotoxins of C. botulinum and C. tetani act as protease. They block the function of peripheral nerves and cause a flaccid paralysis, stimulate adenylate cyclase (cAMP), the high concentration of which causes massive fluid accumulation in the lumen of the gut resulting in watery effect on immune function. Tetanus toxin attacks nerve cells in the CNS and its effects are more dramatic leading to muscle spasm and rigid paralysis.
ADVERTISEMENTS:
The anthrax lethal factor (LF) is a zinc protease that cleaves the N-terminus of MAP (mitogen- activated protein) kinase to inactivate it.
