General Bacterial Toxicology

While we were eating Prof Aung Birthday cake, suddenly he spotted a dot mold on the cake. He was asking about what a fungi could produce and I said " Toxic". Yes, he agrees and ask me how does the toxic could do the living things (at molecular level). As we were scratching our head for the answer (finally couldn't any) but he gave me an idea to find out about how is the toxin effecting to the cells.

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Toxigenesis (ability to produce toxin) is the underlying mechanism by which many bacterial pathogens produce diseases. The 2 main types of toxin

Liposaccharide (Gram-ve bacterial cell wall)
Protein (release from bacterial cells which act on the tissues site)

Cell associated toxin is called endotoxin and extracellular diffusible toxin are referred as exotoxins.

Endotoxin are structural components of bacteria and located mostly at cell envelope. It is specifically refers as lipopolysaccharide (LPS) of lipoologosaccharide (LOS) located at outer membrane of Gram-ve bacteria. Soluble endotoxin released from growing bacteria or from from cell that lysed as a result of self defends mechanism on certain antibiotics.

Exotoxin are usually secreted by bacteria which act on the tissue. Some are secreted by bacterial cell lysis. Exotoxin are usually protein minimally polypeptides act enzymatically or through direct action to the host cell and stimulate variety host responses. Some bacterial exotoxin act at the site of pathogen colonization and play role on invasion.

Example of bacteria produce exotoxin

Clostridium tetani
Corynebacterium diptheriae

The term neurotoxin, enterotoxin, leukotoxin, or hemolysin indicates the action of exotoxin on the specific site. Few bacterial toxin may cause death to the animal (lethal toxins) of which the mechanism is not clear (eg antrax). Some of bacterial toxin utilized as invasin because the act locally to promote bacterial invasion. Example

Collagenase
Hyaluronidase
Streptokinase

Some protein toxin have a very specific cytotoxic activity example tetanus and botulinum attack only neurons but some toxin may have broad cytotoxic acivity (eg Staphylococci, streptococci, clostridia etc)

Bacerial protein toxin are strongly antigenic. Specific antibody neutralizes the toxicity of these bacterial exotoxins. The protein toxins are unstable and may loss toxic properties but retain their antigenicity (toxoids).

Action of antibody to bacterial toxin

Toxin with enzymatic activity

Subunit A+B enzymatic activity

Many protein toxic consists of 2 components (A and B)

A: enzymatic activity

B: binding to specific receptor on the host cell membrane and transferring the enzyme across the membrane.

**The A+B must be complement to transfer the enzyme. If the toxin lacking one of the subunit, they are incapable of infecting the cell.

Attachment entry of toxin

2 mechanism of entry

Direct entry; Subunit B of the native (A+B) tixin binds to a specific receptor on the target cell and induces formation of pore in the membrane through which the A subunit is transfered into the cytoplasm.
Native toxin binds to the target cell and the A+B structure is taken into the cell by the process of receptor-mediated endocytosis (RME). The toxin is internalized in the cell in a membrane-enclosed vesicle called endosome. The H ions enter endosome lowering the internal pH which causes A+B to separate. The B subunit affects the release of the A subunit from the endosome so that it will reach its target in the cell cytoplasm. The subunit B remains in the endosome and is recycled to the cell surface.