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Infect Immun. 2014 Jul;82(7):2958-70. doi: 10.1128/IAI.01848-14. Epub 2014 Apr 28.

Synergistic effects of Clostridium perfringens enterotoxin and beta toxin in rabbit small intestinal loops.

Author information

1
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
2
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA Merck Animal Health, Summit, New Jersey, USA.
3
Animal Health and Food Safety Laboratory System, School of Veterinary Medicine, University of California, Davis, San Bernardino, California, USA.
4
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA Department of Microbiology, Southern Illinois University, Carbondale, Illinois, USA.
5
Animal Health and Food Safety Laboratory System, School of Veterinary Medicine, University of California, Davis, San Bernardino, California, USA fuzal@cahfs.ucdavis.edu.

Abstract

The ability of Clostridium perfringens type C to cause human enteritis necroticans (EN) is attributed to beta toxin (CPB). However, many EN strains also express C. perfringens enterotoxin (CPE), suggesting that CPE could be another contributor to EN. Supporting this possibility, lysate supernatants from modified Duncan-Strong sporulation (MDS) medium cultures of three CPE-positive type C EN strains caused enteropathogenic effects in rabbit small intestinal loops, which is significant since CPE is produced only during sporulation and since C. perfringens can sporulate in the intestines. Consequently, CPE and CPB contributions to the enteropathogenic effects of MDS lysate supernatants of CPE-positive type C EN strain CN3758 were evaluated using isogenic cpb and cpe null mutants. While supernatants of wild-type CN3758 MDS lysates induced significant hemorrhagic lesions and luminal fluid accumulation, MDS lysate supernatants of the cpb and cpe mutants caused neither significant damage nor fluid accumulation. This attenuation was attributable to inactivating these toxin genes since complementing the cpe mutant or reversing the cpb mutation restored the enteropathogenic effects of MDS lysate supernatants. Confirming that both CPB and CPE are needed for the enteropathogenic effects of CN3758 MDS lysate supernatants, purified CPB and CPE at the same concentrations found in CN3758 MDS lysates also acted together synergistically in rabbit small intestinal loops; however, only higher doses of either purified toxin independently caused enteropathogenic effects. These findings provide the first evidence for potential synergistic toxin interactions during C. perfringens intestinal infections and support a possible role for CPE, as well as CPB, in some EN cases.

PMID:
24778117
PMCID:
PMC4097624
DOI:
10.1128/IAI.01848-14
[Indexed for MEDLINE]
Free PMC Article

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