Clostridium perfringens alpha toxin is a toxin produced by the bacterium Clostridium perfringens (C. perfringens) and is responsible for gas gangrene and myonecrosis in infected tissues. The toxin also possesses hemolytic activity.
alpha toxin | |||||||
---|---|---|---|---|---|---|---|
Identifiers | |||||||
Organism | |||||||
Symbol | plc | ||||||
Alt. symbols | phospholipase C, CPE0036, Zn_dep_PLPC | ||||||
Entrez | 988262 | ||||||
PDB | 1CA1 1KHO, 1GYG, 1QM6, 1QMD, 1KHO, 1GYG, 1QM6, 1QMD | ||||||
UniProt | P0C216 | ||||||
Other data | |||||||
EC number | 3.1.4.3 | ||||||
|
This toxin has been shown to be the key virulence factor in infection with C. perfringens; the bacterium is unable to cause disease without this toxin.[1] Further, vaccination against the alpha toxin toxoid protects mice against C. perfringens gas gangrene.[2] As a result, knowledge about the function of this particular protein greatly aids understanding of myonecrosis.[citation needed]
The alpha toxin has remarkable similarity to toxins produced by other bacteria as well as natural enzymes. There is significant homology with phospholipase C enzymes from Bacillus cereus, C. bifermentans, and Listeria monocytogenes.[3] The C terminal domain shows similarity with non-bacterial enzymes such as pancreatic lipase, soybean lipoxygenase, and synaptotagmin I.[4]
The alpha toxin is a zinc metallophospholipase, requiring zinc for activation. First, the toxin binds to a binding site on the cell surface. The C-terminal C2-like PLAT domain binds calcium and allows the toxin to bind to the phospholipid head-groups on the cell surface. The C-terminal domain enters the phospholipid bilayer. The N-terminal domain has phospholipase activity. This property allows hydrolysis of phospholipids such as phosphatidyl choline, mimicking endogenous phospholipase C. The hydrolysis of phosphatidyl choline produces diacylglycerol, which activates a variety of second messenger pathways. The end-result includes activation of arachidonic acid pathway and production of thromboxane A2, production of IL-8, platelet-activating factor, and several intercellular adhesion molecules. These actions combine to cause edema due to increased vascular permeability.[3]