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
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.