Immunization with the C-domain of α-toxin prevents lethal infection, localizes tissue injury, and promotes host response to challenge with Clostridium perfringens

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Immunization with the C-domain of α-toxin prevents lethal infection, localizes tissue injury, and promotes host response to challenge with Clostridium perfringens

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dc.contributor.author Stevens, Dennis L. en_GB
dc.contributor.author Titball, Richard W. en_GB
dc.contributor.author Jepson, Marie en_GB
dc.contributor.author Bayer, Clifford R. en_GB
dc.contributor.author Hayes-Schroer, Susan M. en_GB
dc.contributor.author Bryant, Amy E. en_GB
dc.contributor.department University of Exeter (at the time of publication Richard Titball was at the Defence, Science and Technology Laboratory, Salisbury, UK); Veterans Affairs Medical Center, Boise, US; University of Idaho; Defence, Science and Technology Laboratory; University of Washington en_GB
dc.date.accessioned 2009-01-08T16:36:56Z en_GB
dc.date.accessioned 2011-01-25T11:47:07Z en_US
dc.date.accessioned 2013-03-20T14:49:17Z
dc.date.issued 2004 en_GB
dc.description.abstract Clostridium perfringens gas gangrene is characterized by rapid tissue destruction, impaired host response, and, often, death. Phospholipase C (α-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 α-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. en_GB
dc.identifier.citation 190 (4), pp. 767-773 en_GB
dc.identifier.doi 10.1086/422691 en_GB
dc.identifier.uri http://hdl.handle.net/10036/47201 en_GB
dc.language.iso en en_GB
dc.publisher Published by University of Chicago Press for the Infectious Diseases Society of America en_GB
dc.relation.url http://dx.doi.org/10.1086/422691 en_GB
dc.relation.url http://www.journals.uchicago.edu/doi/abs/10.1086/422691 en_GB
dc.title Immunization with the C-domain of α-toxin prevents lethal infection, localizes tissue injury, and promotes host response to challenge with Clostridium perfringens en_GB
dc.type Article en_GB
dc.date.available 2009-01-08T16:36:56Z en_GB
dc.date.available 2011-01-25T11:47:07Z en_US
dc.date.available 2013-03-20T14:49:17Z
dc.identifier.issn 0022-1899 en_GB
dc.identifier.issn 1537-6613 en_GB
dc.description © 2004 by the Infectious Diseases Society of America. All rights reserved. en_GB
dc.identifier.journal The Journal of Infectious Diseases en_GB


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