RRC ID 38489
Author Nagahama M, Umezaki M, Oda M, Kobayashi K, Tone S, Suda T, Ishidoh K, Sakurai J.
Title Clostridium perfringens iota-toxin b induces rapid cell necrosis.
Journal Infect Immun
Abstract Clostridium perfringens iota-toxin is a binary toxin composed of an enzyme component (Ia) and a binding component (Ib). Each component alone lacks toxic activity, but together they produce cytotoxic effects. We examined the cytotoxicity of iota-toxin Ib in eight cell lines. A431 and A549 cells were susceptible to Ib, but MDCK, Vero, CHO, Caco-2, HT-29, and DLD-1 cells were not. Ib bound and formed oligomers in the membranes of A431 and MDCK cells. However, Ib entered MDCK cells but not A431 cells, suggesting that uptake is essential for cellular survival. Ib also induced cell swelling and the rapid depletion of cellular ATP in A431 and A549 cells but not the insensitive cell lines. In A431 cells, Ib binds and oligomerizes mainly in nonlipid rafts in the membranes. Disruption of lipid rafts by methyl-β-cyclodextrin did not impair ATP depletion or cell death caused by Ib. Ib induced permeabilization by propidium iodide without DNA fragmentation in A431 cells. Ultrastructural studies revealed that A431 cells undergo necrosis after treatment with Ib. Ib caused a disruption of mitochondrial permeability and the release of cytochrome c. Staining with active-form-specific antibodies showed that the proapoptotic Bcl-2-family proteins Bax and Bak were activated and colocalized with mitochondria in Ib-treated A431 cells. We demonstrate that Ib by itself produces cytotoxic activity through necrosis.
Volume 79(11)
Pages 4353-60
Published 2011-11-1
DOI 10.1128/IAI.05677-11
PII IAI.05677-11
PMID 21911469
PMC PMC3257925
MeSH ADP Ribose Transferases / toxicity* Adenosine Triphosphate / metabolism Animals Bacterial Toxins / toxicity* Cell Line Cytochromes c / metabolism Gene Expression Regulation / drug effects Humans Membrane Microdomains / metabolism Mitochondria / drug effects Necrosis / chemically induced* Potassium Proto-Oncogene Proteins c-bcl-2 / genetics Proto-Oncogene Proteins c-bcl-2 / metabolism
IF 3.201
Times Cited 28
Human and Animal Cells A431(RCB0202) A549(RCB0098) CACO-2(RCB0988) Vero(RCB0001) MDCK(RCB0995) CHO