Open AccessClostridium perfringens Delta-Toxin Induces Rapid Cell Necrosis
Author(s) -
Soshi Seike,
Kazuaki Miyamoto,
Kazuo Kobayashi,
Masaya Takehara,
Masahiro Nagahama
Publication year - 2016
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0147957
Subject(s) - clostridium perfringens , toxin , propidium iodide , cytotoxicity , biology , population , cholera toxin , microbiology and biotechnology , chemistry , biochemistry , programmed cell death , apoptosis , medicine , genetics , bacteria , in vitro , environmental health
Clostridium perfringens delta-toxin is a β-pore-forming toxin and a putative pathogenic agent of C . perfringens types B and C. However, the mechanism of cytotoxicity of delta-toxin remains unclear. Here, we investigated the mechanisms of cell death induced by delta-toxin in five cell lines (A549, A431, MDCK, Vero, and Caco-2). All cell lines were susceptible to delta-toxin. The toxin caused rapid ATP depletion and swelling of the cells. Delta-toxin bound and formed oligomers predominantly in plasma membrane lipid rafts. Destruction of the lipid rafts with methyl β-cyclodextrin inhibited delta-toxin-induced cytotoxicity and ATP depletion. Delta-toxin caused the release of carboxyfluorescein from sphingomyelin-cholesterol liposomes and formed oligomers; toxin binding to the liposomes declined with decreasing cholesterol content in the liposomes. Flow cytometric assays with annexin V and propidium iodide revealed that delta-toxin treatment induced an elevation in the population of annexin V-negative and propidium iodide-positive cells. Delta-toxin did not cause the fragmentation of DNA or caspase-3 activation. Furthermore, delta-toxin caused damage to mitochondrial membrane permeability and cytochrome c release. In the present study, we demonstrate that delta-toxin produces cytotoxic activity through necrosis.