''Clostridium perfringens'' beta toxin is one of the four major lethal protein toxins produced by ''

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 an ...

'' Type B and Type C strains. It is a

necrotizing Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...

agent and it induces hypertension by release of

catecholamine A catecholamine (; abbreviated CA) is a monoamine neurotransmitter, an organic compound that has a catechol ( benzene with two hydroxyl side groups next to each other) and a side-chain amine. Catechol can be either a free molecule or a ...

. It has been shown to cause necrotic enteritis in mammals and induces necrotizing intestinal lesions in the rabbit ileal loop model. ''C. perfringens'' beta toxin is susceptible to breakdown by

proteolytic enzymes Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases, ...

, particularly

trypsin Trypsin is an enzyme in the first section of the small intestine that starts the digestion of protein molecules by cutting these long chains of amino acids into smaller pieces. It is a serine protease from the PA clan superfamily, found in the d ...

. Beta toxin is therefore highly lethal to infant mammals because of trypsin inhibitors present in the

colostrum Colostrum, also known as beestings or first milk, is the first form of milk produced by the mammary glands of mammals (including humans) immediately following delivery of the newborn. Colostrum powder is rich in high protein and low in sugar and ...

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

monomer In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization. Classification ...

ic gene product. The larger has a molecular mass of 118 kDa and may be an

oligomer In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relat ...

of smaller units. The first 27 amino acids may encode a signal that allows beta toxin to cross the

cell 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 (the ...

, further evidenced by the presence of beta toxin in extracellular fluid of ''C. perfringens'' cultures.

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 An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conve ...

-selective 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 (th ...

of 1.6–1.8 nm and results in swelling and lysis in HL60 cells. Treatment of these cells with beta toxin induces an efflux of K⁺ and influxes of Ca²⁺, Cl⁻ and Na⁺. 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. Further work on beta toxin has been hampered by its ineffectiveness on many readily available

cell lines An immortalised cell line is a population of cells from a multicellular organism which would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cell ...

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. Enterotoxemia caused by a strains of Type B has been seen in foals in Great Britain and sheep and goats in Iran. Vaccines have been developed to combat lamb dysentery in sheep flocks at high risk.

''C. perfringens'' Type C

Beta toxin is the principal disease causing toxin in ''C. perfringens'' type C infection, and causes necrotizing enteritis and

enterocolitis Enterocolitis is an inflammation of the digestive tract, involving enteritis of the small intestine and colitis of the colon. It may be caused by various infections, with bacteria, viruses, fungi, parasites, or other causes. Common clinical manif ...

. In the disease process, ''C. perfringens'' penetrates the upper

jejunum The jejunum is the second part of the small intestine in humans and most higher vertebrates, including mammals, reptiles, and birds. Its lining is specialised for the absorption by enterocytes of small nutrient molecules which have been previou ...

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. Type C causes fatal hemorrhagic enteritis in neonatal calves in North America but has been particularly prevalent in swine worldwide. 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

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 Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...

of pregnant sows has proven effective at preventing the disease in piglets. Outbreaks in piglets from unvaccinated sows may be treated with oral antibiotics and antiserum.

References

{{reflist, 2 Bacterial toxins