RRC ID 61430
Author Seike S, Miyamoto K, Kobayashi K, Takehara M, Nagahama M.
Title Clostridium perfringens Delta-Toxin Induces Rapid Cell Necrosis.
Journal PLoS One
Abstract 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.
Volume 11(1)
Pages e0147957
Published 2016-1-1
DOI 10.1371/journal.pone.0147957
PII PONE-D-15-34941
PMID 26807591
PMC PMC4726729
MeSH Animals Bacterial Toxins* Caco-2 Cells Caspase 3 / metabolism Cell Death / drug effects* Chlorocebus aethiops DNA Fragmentation / drug effects Fluoresceins / metabolism Humans Membrane Microdomains / drug effects Membrane Microdomains / metabolism Necrosis / chemically induced* Necrosis / metabolism Vero Cells
IF 2.74
Human and Animal Cells A549(RCB0098) A431(RCB0202) CACO-2(RCB0988) Vero(RCB0001) MDCK(RCB0995)