An enterotoxin is a protein exotoxin released by a microorganism that targets the intestines. Enterotoxins are chromosomally encoded or plasmid encoded exotoxins that are produced and secreted from several bacterial organisms. They are heat labile (>60⁰), and are of low molecular weight and water-soluble. Enterotoxins are frequently

cytotoxic Cytotoxicity is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g. from the puff adder (''Bitis arietans'') or brown recluse spider (''Loxosceles reclusa''). Cell physiology Treating cel ...

and kill cells by altering the apical membrane permeability of the mucosal (

epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...

) cells of the intestinal wall. They are mostly pore-forming toxins (mostly chloride pores), secreted by bacteria, that assemble to form pores in

cell membranes The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (the ...

. This causes the cells to die.

Clinical significance

Enterotoxins have a particularly marked effect upon the gastrointestinal tract, causing

traveler's diarrhea Travelers' diarrhea (TD) is a stomach and intestinal infection. TD is defined as the passage of unformed stool (one or more by some definitions, three or more by others) while traveling. It may be accompanied by abdominal cramps, nausea, fever, ...

and food poisoning. The action of enterotoxins leads to increased chloride ion permeability of the

apical membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (th ...

of intestinal mucosal cells. These membrane pores are activated either by increased

cAMP Camp may refer to: Outdoor accommodation and recreation * Campsite or campground, a recreational outdoor sleeping and eating site * a temporary settlement for nomads * Camp, a term used in New England, Northern Ontario and New Brunswick to descri ...

or by increased calcium ion concentration intracellularly. The pore formation has a direct effect on the osmolarity of the luminal contents of the intestines. Increased chloride permeability leads to leakage into the lumen followed by sodium and water movement. This leads to a secretory diarrhea within a few hours of ingesting enterotoxin. Several microbial organisms contain the necessary enterotoxin to create such an effect, such as ''Staphylococcus aureus'' and ''E. coli''. The drug linaclotide, used to treat some forms of constipation, is based on the mechanism of enterotoxins.

Classification and 3D structures

Bacterial

Enterotoxins can be formed by the bacterial pathogens ''Staphylococcus aureus'' and ''Bacillus cereus'' and can cause

Staphylococcal Food Poisoning ''Staphylococcus'' is a genus of Gram-positive bacteria in the family Staphylococcaceae from the order Bacillales. Under the microscope, they appear spherical (cocci), and form in grape-like clusters. ''Staphylococcus'' species are facultati ...

and ''Bacillus cereus'' diarrheal disease, respectively. Staphylococcal enterotoxins and streptococcal exotoxins constitute a family of biologically and structurally related pyrogenic superantigens. 25 staphylococcal enterotoxins (SEs), mainly produced by '' Staphylococcus aureus'', have been identified to date and named alphabetically (SEA - SEZ). It has been suggested that ''staphylococci'' other than ''S. aureus'' can contribute to Staphylococcal Food Poisoning by forming enterotoxins. Streptococcal exotoxins are produced by '' Streptococcus pyogenes''. These toxins share the ability to

bind BIND () is a suite of software for interacting with the Domain Name System (DNS). Its most prominent component, named (pronounced ''name-dee'': , short for ''name daemon''), performs both of the main DNS server roles, acting as an authoritative n ...

to the major histocompatibility complex proteins of their hosts. A more distant relative of the family is the ''S. aureus ''

toxic Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subs ...

shock syndrome toxin, which shares only a low level of sequence similarity with this group. All of these toxins share a similar two-domain fold (N and C-terminal domains) with a long

alpha-helix The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand-helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues ear ...

in the middle of the molecule, a characteristic

beta-barrel In protein structures, a beta barrel is a beta sheet composed of tandem repeats that twists and coils to form a closed toroidal structure in which the first strand is bonded to the last strand (hydrogen bond). Beta-strands in many beta-barrels are ...

known as the "oligosaccharide/oligonucleotide fold" at the N-terminal domain and a beta-grasp motif at the C-terminal domain. An example is

staphylococcal enterotoxin B In the field of molecular biology, enterotoxin type B, also known as Staphylococcal enterotoxin B (SEB), is an enterotoxin produced by the gram-positive bacteria ''Staphylococcus aureus''. It is a common cause of food poisoning, with severe di ...

. Each superantigen possesses slightly different binding mode(s) when it interacts with

MHC class II MHC Class II molecules are a class of major histocompatibility complex (MHC) molecules normally found only on professional antigen-presenting cells such as dendritic cells, mononuclear phagocytes, some endothelial cells, thymic epithelial cells ...

molecules or the

T-cell receptor The T-cell receptor (TCR) is a protein complex found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. The binding b ...

. The beta-grasp domain has some

structural A structure is an arrangement and organization of interrelated elements in a material object or system, or the object or system so organized. Material structures include man-made objects such as buildings and machines and natural objects such as ...

similarities to the beta-grasp motif present in immunoglobulin-binding domains, ubiquitin, 2Fe-2 S ferredoxin and translation initiation factor 3 as identified by the SCOP database. * '' Clostridium difficile'' * ''

Clostridium perfringens ''Clostridium perfringens'' (formerly known as ''C. welchii'', or ''Bacillus welchii'') is a Gram-positive, rod-shaped, anaerobic, spore-forming pathogenic bacterium of the genus ''Clostridium''. ''C. perfringens'' is ever-present in nature and ...

'' ( Clostridium enterotoxin) * '' Vibrio cholerae'' (

Cholera toxin Cholera toxin (also known as choleragen and sometimes abbreviated to CTX, Ctx or CT) is AB5 multimeric protein complex secreted by the bacterium ''Vibrio cholerae''. CTX is responsible for the massive, watery diarrhea characteristic of cholera i ...

) * '' Staphylococcus aureus'' (

Staphylococcal enterotoxin B In the field of molecular biology, enterotoxin type B, also known as Staphylococcal enterotoxin B (SEB), is an enterotoxin produced by the gram-positive bacteria ''Staphylococcus aureus''. It is a common cause of food poisoning, with severe di ...

) * '' Yersinia enterocolitica'' * ''

Shigella dysenteriae ''Shigella dysenteriae'' is a species of the rod-shaped bacterial genus ''Shigella''. ''Shigella'' species can cause shigellosis ( bacillary dysentery). Shigellae are Gram-negative, non-spore-forming, facultatively anaerobic, nonmotile bacte ...

'' ( Shiga toxin)

Viral

Viruses in the families ''

Reoviridae ''Reoviridae'' is a family of double-stranded RNA viruses. Member viruses have a wide host range, including vertebrates, invertebrates, plants, protists and fungi. They lack lipid envelopes and package their segmented genome within multi-layer ...

'', ''

Caliciviridae The ''Caliciviridae'' are a family of "small round structured" viruses, members of Class IV of the Baltimore scheme. Caliciviridae bear resemblance to enlarged picornavirus and was formerly a separate genus within the picornaviridae. They are p ...

'', and ''

Astroviridae ''Astroviridae'' is a family of non-enveloped ssRNA viruses that cause infections in different animals. The family name is derived from the Greek word ''astron'' ("star") referring to the star-like appearance of spikes projecting from the surface ...

'' are responsible for a huge percentage of gastrointestinal disease worldwide. Rotaviruses (of Reoviridae) have been found to contain an enterotoxin which plays a role in viral pathogenesis. NSP4, is a protein that is made during the intracellular phase of the virion's life cycle and is known to have a primary function in intracellular virion maturation. However, when NSP4 from group A Rotaviruses was purified (4 alleles tested), concentrated, and injected into a mouse model, diarrheal disease mimicking that caused by Rotavirus infection commenced. A putative mode of toxicity is that NSP4 activates a signal transduction pathway that ultimately results in an increased cellular concentration of calcium and subsequent chloride secretion from the cell. Secretion of ions from villi lining the gut alter normal osmotic pressures and prevent uptake of water, eventually causing diarrhea. * '' Rotavirus'' ( NSP4)

References

External links