Immunization with the C-Domain of alpha -Toxin prevents lethal infection, localizes tissue injury, and promotes host response to challenge with Clostridium perfringens.
Clostridium perfringens gas gangrene is characterized by rapid tissue destruction, impaired host response, and, often, death. Phospholipase C (alpha -toxin) is the virulence factor most responsible for these pathologies. The present study investigated the efficacy of active immunization with the C-terminal domain of alpha -toxin (Cpa247-370) in a murine model of gas gangrene. Primary end points of the study were survival, progression of infection, and tissue perfusion. Secondary end points, which were based on findings of histologic evaluation of tissues, included the extent of tissue destruction and microvascular thrombosis, as well as the magnitude of the tissue inflammatory response. Survival among C-domain-immunized animals was significantly greater than that among sham-immunized control animals. Furthermore, immunization with the C-domain localized the infection and prevented ischemia of the feet. Histopathologic findings demonstrated limited muscle necrosis, reduced microvascular thrombosis, and enhanced granulocytic influx in C-domain-immunized mice. We conclude that immunization with the C-domain of phospholipase C is a viable strategy for the prevention of morbidity and mortality associated with C. perfringens gas gangrene.
Veterans Affairs Medical Center, Boise, Idaho 83702, USA. dlsteven@mindspring.com
Dennis L
DL
Stevens
Richard W
RW
Titball
Marie
M
Jepson
Clifford R
CR
Bayer
Susan M
SM
Hayes-Schroer
Amy E
AE
Bryant
D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage*; D003016:Clostridium perfringens; D004195:Disease Models, Animal; D005121:Extremities / Q000098:blood supply; D005260:Female; D005738:Gas Gangrene / Q000473:pathology / Q000517:prevention & control*; D007114:Immunization; D007511:Ischemia / Q000517:prevention & control; D051379:Mice; D018482:Muscle, Skeletal / Q000098:blood supply / Q000473:pathology; D009336:Necrosis; D009504:Neutrophils / Q000473:pathology; D013927:Thrombosis / Q000473:pathology; D010738:Type C Phospholipases / Q000008:administration & dosage* / Q000737:chemistry; D014614:Vaccines, Synthetic
D001428:Bacterial Vaccines; D014614:Vaccines, Synthetic; D010738:Type C Phospholipases