Clostridium perfringens Delta-Toxin Induces Rapid Cell Necrosis

PloS One
Soshi SeikeMasahiro Nagahama

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 stu...Continue Reading

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Citations

Apr 25, 2019·Toxins·Soshi SeikeMasahiro Nagahama
Sep 21, 2017·Frontiers in Physiology·Vinod K ChauhanAparna Dutta-Gupta
Jul 14, 2017·Scientific Reports·Teruhisa TakagishiMasahiro Nagahama
Dec 22, 2020·The Journal of Veterinary Medical Science·Akm Azharul IslamMasafumi Mukamoto
May 22, 2019·Microbiology Spectrum·Sarah A Revitt-MillsVicki Adams

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Methods Mentioned

BETA
electrophoresis
enzymatic assay
flow cytometry
confocal microscopy

Software Mentioned

FlowJo
Adobe Photoshop

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