Clostridium perfringens is a Gram-positive, anaerobic, spore-forming rod. It produces at least 12 different toxins, which are broadly classified as “major toxins” and “minor toxins”. Certain strains also produce enterotoxin and neuraminidase. These toxins are responsible for the pathogenesis gas gangrene (myonecrosis), food poisoning, enteritis, and enterotoxemia.
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Table of Contents
Four Major Toxins
- Alpha (α) toxin
- Beta (β) toxin
- Epsilon (ε) toxin
- Iota (ι) toxin
Eight Minor toxins
- Delta (δ) toxin
- Theta (θ) toxin
- Kappa (κ) toxin
- Lambda (λ) toxin
- Mu (μ) toxin
- Nu (ν) toxin
- Gamma (γ) toxin
- Eta (η) toxin
Others:
- Enterotoxin
- Neuraminidase
There are five strains (toxinotypes) of C.perfringens, designated A through E based on the production of 4 major toxins. Each strain produces a unique spectrum of toxins;
| Strain of Clostridium perfringens | Toxins | Disease(s) |
| Type A | Alpha | Myonecrosis in human and animals |
| Type B | Alpha, beta, epsilon | Severe enteritis in young calves, foals, lambs, and piglets. |
| Type C | Alpha, beta | Necrotizing enterocolitis in humans |
| Type D | Alpha, epsilon | Enterotoxemia in sheep and goats and, on rare occasions, in cattle. |
| Type E | Alpha, iota | Enterotoxemia in calves and lambs. |
Role of major toxins of C. perfringens
Alpha (α) toxin: Alpha toxin is a necrotizing toxin produced by all five strains of Clostridium perfringens. The toxin possesses phospholipase C (PLC), sphingomyelinase (SMase) and biological activities causing hemolysis, lethality, and dermonecrosis. Alpha toxin can cause serious acute pulmonary disease, as well as vascular leak, hemolysis, thrombocytopenia and liver damage.
Beta (β) toxin: Beta-toxin is a lethal necrotizing toxin elaborated by C. perfringens type B and C strain. It has been suggested that beta-toxin may play a role as a pore-forming toxin but its cytotoxic activity is not yet established.
Epsilon (ε) toxin: Epsilon toxin (ETX) is produced by Clostridium perfringens type B and D strains. It is a potent pore-forming toxin responsible for the pathogenesis of enterotoxemia of ruminants (mainly in sheep) and might have a role in the pathogenesis of multiple sclerosis in humans.
Iota (ι) toxin: Iota toxin of C. perfringens is known for its lethality, dermonecrosis, and cytotoxicity. It enters host cells and induces toxicity by exploiting the cell’s endogenous pathways.
Rol of minor toxins of C. perfringens
Delta (δ) toxin: one of the three hemolysins released by a number of C. perfringens type C and possibly type B strains
Theta (θ) toxin: Theta toxin is oxygen–labile cytolysin. This toxin can damage blood vessels, resulting in leukostasis, thrombosis, decreased perfusion and tissue hypoxia. Theta toxin also stimulates cytokine release and can cause shock.
kappa (κ) toxin; Clostridial collagenases break the collagen of human and animals. Collagenase enables the bacteria to infiltrate and colonize host tissue. It may play a role in gas gangrene (myonecrosis) pathogenesis but it’s not a major virulence factor for gas gangrene.
lambda (λ) toxin (protease): λ-Toxin can degrade immunoglobulin G, complement C3 component, fibrinogen, fibronectin, and α2-macroglobulin and protect pathogen from both innate or adaptive immune defenses.
mu (μ) toxin (hyaluronidase): It functions as a “spreading factor” by degrading host hyaluronic acid, thus allowing the spread of toxin.
nu (ν) toxin (DNase); The contribution of DNase in the pathogenicity of C. perfringens is not well characterized yet.
gamma (γ) toxin: Mechanism of action not defined.
eta (η) toxin: Mechanism of action not defined.
Neuraminidase: Neuraminidase is a key enzyme for the catabolism of sialic acid-containing oligosaccharides. Red blood cells (RBCs) have a net negative surface charge due to ionized sialic acid. Neuraminidase makes RBCs panagglutinable removing sialic acid, resulting in an increase in blood viscosity and promoting capillary thrombosis.
Enterotoxin: Enterotoxin is the major toxin responsible for human food poisoning. Clostridium perfringens enterotoxin (CPE) is responsible for causing the symptoms of C. perfringens type A food poisoning.
References and further reading
- Savva, C.G., Clark, A.R., Naylor, C.E. et al. The pore structure of Clostridium perfringens epsilon toxin. Nat Commun 10, 2641 (2019).
- Sakurai J, Nagahama M, Oda M, Tsuge H, Kobayashi K. Clostridium perfringens iota-toxin: structure and function. Toxins (Basel). 2009;1(2):208–228.
- Koneman’s Color Atlas and Textbook of Diagnostic Microbiology