An enterotoxin is a protein

exotoxin An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, simi ...

released by a microorganism that targets the intestines. Enterotoxins are chromosomally encoded or plasmid encoded

s 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 cells ...

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

. This causes the cells to die.

Clinical significance

Enterotoxins have a particularly marked effect upon the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...

, causing traveler's diarrhea 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 (t ...

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 Linaclotide, (sold under the brand name Linzess in the US and Mexico, and as Constella elsewhere) is a drug used to treat irritable bowel syndrome with constipation and chronic constipation with no known cause. For label updates seFDA index page ...

, 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 facultativ ...

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 ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive ...

'', 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 to the

major histocompatibility complex The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are calle ...

proteins of their hosts. A more distant relative of the family is the ''S. aureus '' toxic 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 Fold, folding or foldable may refer to: Arts, entertainment, and media * ''Fold'' (album), the debut release by Australian rock band Epicure *Fold (poker), in the game of poker, to discard one's hand and forfeit interest in the current pot *Above ...

(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 known as the "oligosaccharide/oligonucleotide fold" at the N-terminal

domain Domain may refer to: Mathematics *Domain of a function, the set of input values for which the (total) function is defined **Domain of definition of a partial function **Natural domain of a partial function **Domain of holomorphy of a function * Do ...

and a beta-grasp

motif Motif may refer to: General concepts * Motif (chess composition), an element of a move in the consideration of its purpose * Motif (folkloristics), a recurring element that creates recognizable patterns in folklore and folk-art traditions * Moti ...

at the C-terminal domain. An example is staphylococcal enterotoxin B. Each superantigen possesses slightly different binding mode(s) when it

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

s with MHC class II molecules or the T-cell receptor. The beta-grasp domain has some structural similarities to the beta-grasp

present in immunoglobulin-binding domains, ubiquitin, 2Fe-2 S

ferredoxin Ferredoxins (from Latin ''ferrum'': iron + redox, often abbreviated "fd") are iron–sulfur proteins that mediate electron transfer in a range of metabolic reactions. The term "ferredoxin" was coined by D.C. Wharton of the DuPont Co. and applied t ...

and translation

initiation factor Initiation factors are proteins that bind to the small subunit of the ribosome during the initiation of translation, a part of protein biosynthesis. Initiation factors can interact with repressors to slow down or prevent translation. They have the ...

3 as identified by the

SCOP database The Structural Classification of Proteins (SCOP) database is a largely manual classification of protein structural domains based on similarities of their structures and amino acid sequences. A motivation for this classification is to determine t ...

. * ''

Clostridium difficile ''Clostridioides difficile'' (syn. ''Clostridium difficile'') is a bacterium that is well known for causing serious diarrheal infections, and may also cause colon cancer. Also known as ''C. difficile'', or ''C. diff'' (), is Gram-positive spec ...

'' * '' Clostridium perfringens'' (

Clostridium enterotoxin Clostridium enterotoxins are toxins produced by ''Clostridium'' species. Clostridial species are one of the major causes of food poisoning/gastrointestinal illnesses. They are anaerobic, gram-positive, spore-forming rods that occur naturally in t ...

) * '' Vibrio cholerae'' ( Cholera toxin) * ''

'' ( Staphylococcal enterotoxin B) * '' 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 bacteri ...

'' ( Shiga toxin)

Viral

Viruses in the families '' Reoviridae'', ''

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