Clostridium perfringens alpha-toxin is a key mediator of gas gangrene, which is a life-threatening infection that manifests as fever, pain, edema, myonecrosis, and gas production. Alpha-toxin possesses phospholipase C and sphingomyelinase activities. The toxin is composed of an N-terminal domain (1-250 aa, N-domain), which is the catalytic site, and a C-terminal domain (251-370 aa, C-domain), w...

Alpha toxin from Clostridium perfringens type A, a phospholipase C, has been implicated in many of the localized and systemic features of gas gangrene. We demonstrated that human endothelial cells synthesize two vasoactive lipids, platelet-activating factor (PAF) and prostacyclin, in response to alpha toxin treatment. The stimulated synthesis of PAF required the enzymatic activity of the toxin ...

Necrotic enteritis (NE) in poultry has re-emerged as a concern for poultry producers, due in part to banning, by many countries, of the use of antimicrobial growth promoters in feeds. This re-emergence has led to a search for alternative methods for control of the disease, particularly vaccination. The objective of this work was to determine if vaccination of broiler chicks with recombinant alp...

Intracellular Staphylococcus aureus has been implicated in the establishment of chronic infections. It is therefore imperative to understand by what means S. aureus is able to survive within cells. Here we use two expression systems with a fluorescent readout to assay alpha-toxin expression and function within phagolysosomes of infected upper-airway epithelial cells: avirulent Staphylococcus ca...

De Gascun and colleagues report on a case of methicillinsusceptible Staphylococcus aureus (MSSA) sepsis treated successfully with linezolid after initial failure of a triple regimen of apparently appropriate antibiotics. They ascribe the observed efficacy of linezolid to an anti-toxin effect of the antibiotic. Linezolid acts by inhibiting bacterial protein synthesis, and it, therefore, blocks t...

Aspirin has been reported to inhibit the activation of nuclear factor-kappaB (NF-kappaB) through stabilization of inhibitor kappaB (IkappaB). This observation led us to investigate the role of aspirin in suppressing the activation of the NF-kappaB-regulated tumor necrosis factor-alpha (TNF-alpha) gene expression in primary macrophages. We now report that therapeutic doses of aspirin suppress li...

Clostridium septicum produces a number of diseases in human and farm animals which, in most of the cases, are fatal without clinical intervention. Alpha toxin is an important agent and the unique lethal virulent factor produced by Clostridium septicum. This toxin is haemolytic, highly lethal and necrotizing activities but is being used as an antigen to develop animal vaccines. The aim of this s...

The phospholipases C of C. perfringens (alpha-toxin) and C. bifermentans (Cbp) show >50% amino acid homology but differ in their hemolytic and toxic properties. We report here the purification and characterisation of alpha-toxin and Cbp. The phospholipase C activity of alpha-toxin and Cbp was similar when tested with phosphatidylcholine in egg yolk or in liposomes. However, the hemolytic activi...

McClatchy, J. K. (The University of Texas Southwestern Medical School, Dallas), and E. D. Rosenblum. Biological properties of alpha-toxin mutants of Staphylococcus aureus. J. Bacteriol. 92:575-579. 1966.-Twenty nonhemolytic mutants of Staphylococcus aureus were isolated after treatment of a hemolytic strain with ultraviolet light or nitrous acid. Thirteen strains isolated were completely lackin...

Clostridium perfringens alpha-toxin elicits various immune responses such as the release of cytokines, chemokines, and superoxide via the GM1a/TrkA complex. Alpha-toxin possesses phospholipase C (PLC) hydrolytic activity that contributes to signal transduction in the pathogenesis of gas gangrene. Little is known about the relationship between lipid metabolism and TrkA activation by alpha-toxin....