ROLE OF THETA-TOXIN, A SULFHYDRYL-ACTIVATED CYTOLYSIN, IN THE PATHOGENESIS OF CLOSTRIDIAL GAS-GANGRENE

Citation
Dl. Stevens et Ae. Bryant, ROLE OF THETA-TOXIN, A SULFHYDRYL-ACTIVATED CYTOLYSIN, IN THE PATHOGENESIS OF CLOSTRIDIAL GAS-GANGRENE, Clinical infectious diseases, 16, 1993, pp. 190000195-190000199
Citations number
13
Categorie Soggetti
Microbiology,Immunology
ISSN journal
10584838
Volume
16
Year of publication
1993
Supplement
4
Pages
190000195 - 190000199
Database
ISI
SICI code
1058-4838(1993)16:<190000195:ROTASC>2.0.ZU;2-A
Abstract
Clostridial infections cause a wide variety of dramatic infections and intoxications. In each case the major virulence factors are extracell ular toxins. Clostridium perfringens produces potent exotoxins, which are its major virulence factors. Theta Toxin, a thiol-activated cytoly sin, causes the clear zone of hemolysis around colonies on blood-agar plates, suppresses myocardial contractility ex vivo, and induces shock within 1 to 2 hours in vivo. Low concentrations of theta toxin induce priming and degranulation of polymorphonuclear leukocytes (PMNs) and functional up-regulation of PMN-dependent adherence molecules such as the integrin CD11/CD18, whereas higher concentrations are cytotoxic. S imilarly, theta toxin causes concentration- and time-dependent inducti on of endothelial cell synthesis of platelet-activating factor, a pote nt proinflammatory lipid autocoid that mediates endothelial cell-depen dent adherence of PMNs. These data suggest that theta toxin in high co ncentrations is a potent cytolysin and promotes direct vascular injury at the site of infection. At lower concentrations theta toxin activat es PMNs and endothelial cells, and in so doing promotes vascular injur y distally by activating adherence mechanisms. The rapid tissue necros is associated with C. perfringens infection may be related to progress ive vascular compromise orchestrated by dysregulated host-cell respons es induced by theta toxin.