Identification of residues critical for toxicity in Clostridium perfringens phospholipase C, the key toxin in gas gangrene
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| Autores: | , , , , , , , , , , |
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| Formato: | artículo original |
| Fecha de Publicación: | 2000 |
| Descripción: | Clostridium perfringens phospholipase C (PLC), also called α-toxin, is the major virulence factor in the pathogenesis of gas gangrene. The toxic activities of genetically engineered α-toxin variants harboring single amino-acid substitutions in three loops of its C-terminal domain were studied. The substitutions were made in aspartic acid residues which bind calcium, and tyrosine residues of the putative membrane-interacting region. The variants D269N and D336N had less than 20% of the hemolytic activity and displayed a cytotoxic potency 103-fold lower than that of the wild-type toxin. The variants in which Tyr275, Tyr307, and Tyr331 were substituted by Asn, Phe, or Leu had 11–73% of the hemolytic activity and exhibited a cytotoxic potency 102- to 105-fold lower than that of the wild-type toxin. The results demonstrated that the sphingomyelinase activity and the C-terminal domain are required for myotoxicity in vivo and that the variants D269N, D336N, Y275N, Y307F, and Y331L had less than 12% of the myotoxic activity displayed by the wild-type toxin. This work therefore identifies residues critical for the toxic activities of C. perfringens PLC and provides new insights toward understanding the mechanism of action of this toxin at a molecular level. |
| País: | Kérwá |
| Institución: | Universidad de Costa Rica |
| Repositorio: | Kérwá |
| OAI Identifier: | oai:https://www.kerwa.ucr.ac.cr:10669/29468 |
| Acceso en línea: | http://onlinelibrary.wiley.com/doi/10.1046/j.1432-1327.2000.01588.x/abstract;jsessionid=C9CB49492B0F301FFEFD4283817CDE46.f03t01 https://hdl.handle.net/10669/29468 |
| Access Level: | acceso abierto |
| Palabra clave: | Bacterial Toxins Muscular Diseases Molecular Models Skeletal Muscle Cell Survival |