Document Detail


A cellular deficiency of gangliosides causes hypersensitivity to Clostridium perfringens phospholipase C.
MedLine Citation:
PMID:  15919667     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Clostridium perfringens phospholipase C (Cp-PLC), also called alpha-toxin, is the major virulence factor in the pathogenesis of gas gangrene. Previously, a cellular UDP-Glc deficiency was related with a hypersensitivity to the cytotoxic effect of Cp-PLC. Because UDP-Glc is required in the synthesis of proteoglycans, N-linked glycoproteins, and glycosphingolipids, the role of these gly-coconjugates in the cellular sensitivity to Cp-PLC was studied. The cellular sensitivity to Cp-PLC was significantly enhanced by glycosphingolipid synthesis inhibitors, and a mutant cell line deficient in gangliosides was found to be hypersensitive to Cp-PLC. Gangliosides protected hypersensitive cells from the cytotoxic effect of Cp-PLC and prevented its membrane-disrupting effect on artificial membranes. Removal of sialic acids by C. perfringens sialidase increases the sensitivity of cultured cells to Cp-PLC and intramuscular co-injection of C. perfringens sialidase, and Cp-PLC in mice potentiates the myotoxic effect of the latter. This work demonstrated that a reduction in gangliosides renders cells more susceptible to the membrane damage caused by Cp-PLC and revealed a previously unrecognized synergism between Cp-PLC and C. perfringens sialidase, providing new insights toward understanding the pathogenesis of clostridial myonecrosis.
Authors:
Marietta Flores-Díaz; Alberto Alape-Girón; Graeme Clark; Bruno Catimel; Yoshio Hirabayashi; Ed Nice; José-María Gutiérrez; Richard Titball; Monica Thelestam
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-05-26
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  280     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-07-19     Completed Date:  2005-09-09     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  26680-9     Citation Subset:  IM    
Affiliation:
Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm S-17177, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cell Membrane / drug effects
Clostridium perfringens / enzymology,  immunology*,  pathogenicity
Drug Synergism
Gangliosides / deficiency*,  physiology
Humans
Hypersensitivity / etiology*
Liposomes
Mice
Neuraminidase / administration & dosage,  pharmacology
Sialic Acids
Type C Phospholipases / administration & dosage,  immunology*,  pharmacology
Chemical
Reg. No./Substance:
0/Gangliosides; 0/Liposomes; 0/Sialic Acids; EC 3.1.4.-/Type C Phospholipases; EC 3.2.1.18/Neuraminidase

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