Cellular mechanism of toxicity of Clostridium perfringens iota-toxin

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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. This study indicated that an internalized Ia and Ib complex was delivered to early endosomes and that subsequent delivery of Ia to the cytoplasm occured mainly in early endosomes. Then, Ib was transported to late endosomes and lysosomes for degradation. Next, we examined the cytotoxicity of Ib. A431 and A549 cells were susceptible to Ib. Ib bound and formed oligomers in the membranes of A431 cells. Then, Ib caused cell swelling and the rapid depletion of cellular ATP in the cells. Ib also induced permeabilization by propidium iodide without DNA fragmentation in the cells. Ultrastructural studies revealed that A431 cells underwent necrosis after treatment with Ib. We demonstrated that Ib by itself produced cytotoxic activity through necrosis.