In vitro cytotoxicity induced by Clostridium perfringens isolate carrying a chromosomal cpe gene is exclusively dependent on sporulation and enterotoxin production Public Deposited

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  • Clostridium perfringens type A is a common source of food poisoning (FP) and non-food-borne (NFB) gastrointestinal diseases in humans. In the intestinal tract, the vegetative cells sporulate and produce a major pathogenic factor, C. perfringens enterotoxin (CPE). Most type A FP isolates carry a chromosomal cpe gene, whereas NFB type A isolates typically carry a plasmid-encoded cpe. In vitro, the purified CPE protein binds to a receptor and forms pores, exerting a cytotoxic activity in epithelial cells. However, it remains unclear if CPE is indispensable for C. perfringens cytotoxicity. In this study, we examined the cytotoxicity of cpe-harboring C. perfringens isolates co-cultured with human intestinal epithelial Caco-2 cells. The FP strains showed severe cytotoxicity during sporulation and CPE production, but not during vegetative cell growth. While Caco-2 cells were intact during co-culturing with cpe-null mutant derivative of strain SM101 (a FP strain carrying a chromosomal cpe gene), the wild-type level cytotoxicity was observed with cpe-complemented strain. In contrast, both wild-type and cpe-null mutant derivative of the NFB strain F4969 induced Caco-2 cell death during both vegetative and sporulation growth. Collectively, the Caco-2 cell cytotoxicity caused by C. perfringens strain SM101 is considered to be exclusively dependent on CPE production, whereas some additional toxins should be involved in F4969-mediated in vitro cytotoxicity.
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  • Yasugi, M., Sugahara, Y., Hoshi, H., Kondo, K., Talukdar, P. K., Sarker, M. R., ... & Miyake, M. (2015). In vitro cytotoxicity induced by Clostridium perfringens isolate carrying a chromosomal cpe gene is exclusively dependent on sporulation and enterotoxin production. Microbial Pathogenesis, 85, 1-10. doi:10.1016/j.micpath.2015.04.003
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  • 85
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  • This work was supported in part by JSPS KAKENHI (grant number 25860467) to M.Y., a grant from the Takeda Science Foundation to M.Y., a Health Sciences Research Grant from the Ministry of Health, Labor and Welfare of Japan201327009A to Y.K. and M.M., a Department of Defense Multidisciplinary University Research Initiative (MURI) award through the U.S. Army Research Laboratory, and the U.S. Army Research Office under contract number W911NF-09-1-0286 to M.R.S.
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