Both epsilon-toxin and beta-toxin are important for the lethal properties of Clostridium perfringens type b isolates in the mouse intravenous injection model

M E Fernandez-Miyakawa, Derek J Fisher, Rachael Poon, Sameera Sayeed, Victoria Michelle Adams, Julian Ian Rood, Bruce A McClane, Francisco A Uzal

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Abstract

Clostridium perfringens is capable of producing up to 15 toxins, including alpha toxin (CPA), beta toxin (CPB), epsilon toxin (ETX), enterotoxin (CPE), beta2 toxin (CPB2), and perfringolysin O (PFO). Type B isolates, which must produce CPA, CPB, and ETX, are associated with animal illnesses characterized by sudden death or acute neurological signs, with or without intestinal damage. Type B pathogenesis in ruminants is poorly understood, with some animals showing lesions and clinical signs similar to either type C or D infections. It is unknown whether host or environmental conditions are dominant for determining the outcome of type B disease or if disease outcomes are determined by variable characteristics of type B isolates. To help clarify this issue, 29 type B isolates were evaluated for toxin production during late log-phase growth via quantitative Western blotting and by biological activity assays. Most type B isolates produced similar CPB levels to type C isolates in vitro, and have the potential to produce genotype C-like disease. The lethality of type B isolate supernatants administered intravenously to mice was evaluated with or without prior trypsin treatment and monoclonal antibody neutralization studies also were performed. Correlation analyses comparing toxin levels in type B supernatants versus lethality and neutralization studies both found that the main contributor to lethality without pre-treatment with trypsin was CPB, whereas neutralization studies indicated that CPB and ETX were both important after trypsin pre-treatment. At least part of the CPB produced by type B isolates remained active after trypsin treatment.
Original languageEnglish
Pages (from-to)1443 - 1452
Number of pages10
JournalInfection and Immunity
Volume75
Issue number3
Publication statusPublished - 2007

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