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Infect Immun, June 1998, p. 2660-2665, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Clostridium difficile Toxin B Induces Apoptosis in Intestinal Cultured Cells

Carla Fiorentini,* Alessia Fabbri, Loredana Falzano, Andrea Fattorossi, Paola Matarrese, Roberto Rivabene, and Gianfranco Donelli

Department of Ultrastructures, Istituto Superiore di Sanità, 00161 Rome, Italy

Received 19 December 1997/Returned for modification 13 February 1998/Accepted 30 March 1998

Toxigenic strains of the anaerobic bacterium Clostridium difficile produce at least two large, single-chain protein exotoxins involved in the pathogenesis of antibiotic-associated diarrhea and colitis. Toxin A (CdA) is a cytotoxic enterotoxin, while toxin B (CdB) is a more potent cytotoxin lacking enterotoxic activity. This study dealt with CdB, providing the first evidence that intestinal cells exposed to this toxin exhibit typical features of apoptosis in that a significant proportion of the treated cells displayed nuclear fragmentation and chromatin condensation. In keeping with ultrastructural data, CdB-treated cells showed the typical flow cytometric hallmark of apoptosis consisting of a distinct sub-G1 peak. The CdB-induced apoptotic response was dose and time dependent and not simply due to the actin-disrupting effect of the toxin or to the subsequent impairment of cell anchorage. Rather, the inhibition of proteins belonging to the Rho family due to CdB seems to play a role in the induction of apoptosis in intestinal cells. The origin of cells and the growth rate may also be cofactors relevant to such a response.

* Corresponding author. Mailing address: Department of Ultrastructures, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy. Phone: 39-6-49903006. Fax: 39-6-49387140. E-mail: fiorentini{at}ul.net.iss.it.

Infect Immun, June 1998, p. 2660-2665, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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