Clostridium perfringens beta toxin

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Beta toxin
Identifiers
Organism Clostridium perfringens
Symbolcpb
Alt. symbolsα-hemolysin, hlgB_2
UniProt Q46181
Search for
Structures Swiss-model
Domains InterPro

Clostridium perfringens beta toxin is one of the four major lethal protein toxins produced by Clostridium perfringens Type B and Type C strains. [1] It is a necrotizing agent and it induces hypertension by release of catecholamine. It has been shown to cause necrotic enteritis in mammals and induces necrotizing intestinal lesions in the rabbit ileal loop model. [2] C. perfringens beta toxin is susceptible to breakdown by proteolytic enzymes, particularly trypsin. [3] Beta toxin is therefore highly lethal to infant mammals because of trypsin inhibitors present in the colostrum. [3]

Contents

Structure and homology

Clostridium perfringens beta toxin shows significant genetic homology with several other toxins. C. perfringens beta toxin shows 28% homology with S. aureus alpha toxin and similar homology to S. aureus gamma-toxin and leukocidin. It appears in two forms. The smaller, with a molecular mass of 34 kDa, represents the monomeric gene product. The larger has a molecular mass of 118 kDa and may be an oligomer of smaller units. The first 27 amino acids may encode a signal that allows beta toxin to cross the cell membrane, further evidenced by the presence of beta toxin in extracellular fluid of C. perfringens cultures. [1]

Function

Pore formation

Because C. perfringens beta toxin shares homology with S. aureus pore-forming alpha toxin, it was hypothesized that beta toxin acts in a similar way. Upon investigation, it was found that C. perfringens beta toxin forms cation-selective pores in cell membranes [4] of 1.61.8 nm [5] and results in swelling and lysis in HL60 cells. [6] Treatment of these cells with beta toxin induces an efflux of K+ and influxes of Ca2+, Cl and Na+. [6] Heat-stable beta-toxin oligomers are shown to bind to cell membranes of human umbilical vein endothelial cells; endothelial cells are beta toxin's primary target, upon introduction. [4] Further work on beta toxin has been hampered by its ineffectiveness on many readily available cell lines. [4] [6]

Clinical significance

C. perfringens Type B

Beta toxin is the principal disease causing toxin in C. perfringens type B infection. Type B has caused lamb dysentery in Great Britain and South Africa. [7] Enterotoxemia caused by a strains of Type B has been seen in foals in Great Britain and sheep and goats in Iran. [7] Vaccines have been developed to combat lamb dysentery in sheep flocks at high risk. [7]

C. perfringens Type C

Beta toxin from C. perfringens type C is highly lethal to neonatal pigs and occurs worldwide in farmed pigs. Oregon State Fair pigs.jpg
Beta toxin from C. perfringens type C is highly lethal to neonatal pigs and occurs worldwide in farmed pigs.

Beta toxin is the principal disease causing toxin in C. perfringens type C infection, and causes necrotizing enteritis and enterocolitis. In the disease process, C. perfringens penetrates the upper jejunum between absorptive cells and releases beta toxin. Beta toxin causes necrosis of the villi and mucosa, often causing blood loss into the lumen and intestinal wall. [8] Type C causes fatal hemorrhagic enteritis in neonatal calves in North America [7] but has been particularly prevalent in swine worldwide. [9] It is primarily fatal to animals 1–3 days old, whose digestive enzymes may not be sufficiently active to break down beta toxin. It has been experimentally shown that trypsin may normally break down beta toxin, and trypsin shortages in the digestive system of experimental animals have been used to induce type C disease. Vaccination of pregnant sows has proven effective at preventing the disease in piglets. [8] [9] Outbreaks in piglets from unvaccinated sows may be treated with oral antibiotics and antiserum. [8]

See also

Related Research Articles

<span class="mw-page-title-main">Gangrene</span> Type of tissue death by a lack of blood supply

Gangrene is a type of tissue death caused by a lack of blood supply. Symptoms may include a change in skin color to red or black, numbness, swelling, pain, skin breakdown, and coolness. The feet and hands are most commonly affected. If the gangrene is caused by an infectious agent, it may present with a fever or sepsis.

<span class="mw-page-title-main">Necrotizing fasciitis</span> Infection that results in the death of the bodys soft tissue

Necrotizing fasciitis (NF), also known as flesh-eating disease, is a bacterial infection that results in the death of parts of the body's soft tissue. It is a severe disease of sudden onset that spreads rapidly. Symptoms usually include red or purple skin in the affected area, severe pain, fever, and vomiting. The most commonly affected areas are the limbs and perineum.

<i>Clostridium perfringens</i> Species of bacterium

Clostridium perfringens is a Gram-positive, rod-shaped, anaerobic, spore-forming pathogenic bacterium of the genus Clostridium. C. perfringens is ever-present in nature and can be found as a normal component of decaying vegetation, marine sediment, the intestinal tract of humans and other vertebrates, insects, and soil. It has the shortest reported generation time of any organism at 6.3 minutes in thioglycolate medium.

<span class="mw-page-title-main">Exotoxin</span> Toxin from bacteria that destroys or disrupts cells

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, similar to endotoxins, may be released during lysis of the cell. Gram negative pathogens may secrete outer membrane vesicles containing lipopolysaccharide endotoxin and some virulence proteins in the bounding membrane along with some other toxins as intra-vesicular contents, thus adding a previously unforeseen dimension to the well-known eukaryote process of membrane vesicle trafficking, which is quite active at the host–pathogen interface.

Enteritis is inflammation of the small intestine. It is most commonly caused by food or drink contaminated with pathogenic microbes, such as Serratia, but may have other causes such as NSAIDs, radiation therapy as well as autoimmune conditions like Crohn's disease and celiac disease. Symptoms include abdominal pain, cramping, diarrhea, dehydration, and fever. Related diseases of the gastrointestinal system include inflammation of the stomach and large intestine.

<span class="mw-page-title-main">Enterotoxin</span> Toxin from a microorganism affecting the intestines

An enterotoxin is a protein exotoxin released by a microorganism that targets the intestines. They can be chromosomally or plasmid encoded. They are heat labile (>60⁰), of low molecular weight and water-soluble. Enterotoxins are frequently cytotoxic and kill cells by altering the apical membrane permeability of the mucosal (epithelial) cells of the intestinal wall. They are mostly pore-forming toxins, secreted by bacteria, that assemble to form pores in cell membranes. This causes the cells to die.

<span class="mw-page-title-main">Gas gangrene</span> Human bacterial infection

Gas gangrene is a bacterial infection that produces tissue gas in gangrene. This deadly form of gangrene usually is caused by Clostridium perfringens bacteria. About 1,000 cases of gas gangrene are reported yearly in the United States.

Lecithinase is a type of phospholipase that acts upon lecithin.

Cytolysin refers to the substance secreted by microorganisms, plants or animals that is specifically toxic to individual cells, in many cases causing their dissolution through lysis. Cytolysins that have a specific action for certain cells are named accordingly. For instance, the cytolysins responsible for the destruction of red blood cells, thereby liberating hemoglobins, are named hemolysins, and so on. Cytolysins may be involved in immunity as well as in venoms.

Clostridial necrotizing enteritis (CNE) is a severe and potentially fatal type of food poisoning caused by a β-toxin of Clostridium perfringens, Type C. It occurs in some developing regions, particularly in New Guinea, where it is known as pig-bel. The disease was also documented in Germany following World War II, where it was called Darmbrand (literally "bowel fire," or bowel necrosis). The toxin is normally inactivated by certain proteolytic enzymes and by normal cooking, but when these protections are impeded by diverse factors, and high protein is consumed, the disease can emerge.

<i>Clostridium perfringens</i> alpha toxin Toxin produced by the bacterium Clostridium perfringens

Clostridium perfringens alpha toxin is a toxin produced by the bacterium Clostridium perfringens and is responsible for gas gangrene and myonecrosis in infected tissues. The toxin also possesses hemolytic activity.

<span class="mw-page-title-main">Pore-forming toxin</span> Protein-produced toxins that create pores in cell membrane

Pore-forming proteins are usually produced by bacteria, and include a number of protein exotoxins but may also be produced by other organisms such as apple snails that produce perivitellin-2 or earthworms, who produce lysenin. They are frequently cytotoxic, as they create unregulated pores in the membrane of targeted cells.

A leukocidin is a type of cytotoxin created by some types of bacteria (Staphylococcus). It is a type of pore-forming toxin. The model for pore formation is step-wise. First, the cytotoxin’s “S” subunit recognizes specific protein-containing receptors, or an integrin on the host cell’s surface. The S subunit then recruits a second, “F” subunit, and the two subunits dimerize on the surface of the host’s cell. After dimerization, oligomerization occurs. Finally, the oligomers, consisting of alternating S and F subunits, undergo a significant structural change and form a beta-barrel, that pierces through the host cell’s lipid bilayer.

<i>Staphylococcus aureus</i> alpha toxin

Alpha-toxin, also known as alpha-hemolysin (Hla), is the major cytotoxic agent released by bacterium Staphylococcus aureus and the first identified member of the pore forming beta-barrel toxin family. This toxin consists mostly of beta-sheets (68%) with only about 10% alpha-helices. The hly gene on the S. aureus chromosome encodes the 293 residue protein monomer, which forms heptameric units on the cellular membrane to form a complete beta-barrel pore. This structure allows the toxin to perform its major function, development of pores in the cellular membrane, eventually causing cell death.

<span class="mw-page-title-main">Phospholipase C</span> Class of enzymes

Phospholipase C (PLC) is a class of membrane-associated enzymes that cleave phospholipids just before the phosphate group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which play an important role in eukaryotic cell physiology, in particular signal transduction pathways. Phospholipase C's role in signal transduction is its cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into diacyl glycerol (DAG) and inositol 1,4,5-trisphosphate (IP3), which serve as second messengers. Activators of each PLC vary, but typically include heterotrimeric G protein subunits, protein tyrosine kinases, small G proteins, Ca2+, and phospholipids.

<i>Clostridium septicum</i> Species of bacterium

Clostridium septicum is a gram positive, spore forming, obligate anaerobic bacterium.

Microbial toxins are toxins produced by micro-organisms, including bacteria, fungi, protozoa, dinoflagellates, and viruses. Many microbial toxins promote infection and disease by directly damaging host tissues and by disabling the immune system. Endotoxins most commonly refer to the lipopolysaccharide (LPS) or lipooligosaccharide (LOS) that are in the outer plasma membrane of Gram-negative bacteria. The botulinum toxin, which is primarily produced by Clostridium botulinum and less frequently by other Clostridium species, is the most toxic substance known in the world. However, microbial toxins also have important uses in medical science and research. Currently, new methods of detecting bacterial toxins are being developed to better isolate and understand these toxin. Potential applications of toxin research include combating microbial virulence, the development of novel anticancer drugs and other medicines, and the use of toxins as tools in neurobiology and cellular biology.

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References

  1. 1 2 Hunter SE, Brown JE, Oyston PC, Sakurai J, Titball RW (September 1993). "Molecular genetic analysis of beta-toxin of Clostridium perfringens reveals sequence homology with alpha-toxin, gamma-toxin, and leukocidin of Staphylococcus aureus". Infection and Immunity. 61 (9): 3958–3965. doi:10.1128/iai.61.9.3958-3965.1993. PMC   281100 . PMID   8359918.
  2. Miclard J, Jäggi M, Sutter E, Wyder M, Grabscheid B, Posthaus H (June 2009). "Clostridium perfringens beta-toxin targets endothelial cells in necrotizing enteritis in piglets". Veterinary Microbiology. 137 (3–4): 320–325. doi:10.1016/j.vetmic.2009.01.025. PMID   19216036.
  3. 1 2 Garcia JP, Beingesser J, Fisher DJ, Sayeed S, McClane BA, Posthaus H, Uzal FA (June 2012). "The effect of Clostridium perfringens type C strain CN3685 and its isogenic beta toxin null mutant in goats". Veterinary Microbiology. 157 (3–4): 412–419. doi:10.1016/j.vetmic.2012.01.005. PMC   3348370 . PMID   22296994.
  4. 1 2 3 Steinthorsdottir V, Halldórsson H, Andrésson OS (January 2000). "Clostridium perfringens beta-toxin forms multimeric transmembrane pores in human endothelial cells". Microbial Pathogenesis. 28 (1): 45–50. doi:10.1006/mpat.1999.0323. PMID   10623563.
  5. Nagahama M, Hayashi S, Morimitsu S, Sakurai J (September 2003). "Biological activities and pore formation of Clostridium perfringens beta toxin in HL 60 cells". The Journal of Biological Chemistry. 278 (38): 36934–36941. doi: 10.1074/jbc.m306562200 . PMID   12851396.
  6. 1 2 3 Nagahama M, Hayashi S, Morimitsu S, Sakurai J (September 2003). "Biological activities and pore formation of Clostridium perfringens beta toxin in HL 60 cells". The Journal of Biological Chemistry. 278 (38): 36934–36941. doi: 10.1074/jbc.M306562200 . PMID   12851396.
  7. 1 2 3 4 Niilo L (May 1980). "Clostridium perfringens in animal disease: a review of current knowledge". The Canadian Veterinary Journal. 21 (5): 141–148. PMC   1789702 . PMID   6253040.
  8. 1 2 3 "Clostridium perfingens type C enteritis". The Merck Veterinary Handbook. Merck Sharp & Dohme Corp.
  9. 1 2 Niilo L (August 1988). "Clostridium perfringens Type C Enterotoxemia". The Canadian Veterinary Journal. 29 (8): 658–664. PMC   1680772 . PMID   17423103.