Clostridium difficile toxin B induces apoptosis in intestinal cultured cells.
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.
Fiorentini
C
C
Department of Ultrastructures, Istituto Superiore di Sanità, 00161 Rome, Italy. fiorentini@ul.net.iss.it
Fabbri
A
A
Falzano
L
L
Fattorossi
A
A
Matarrese
P
P
Rivabene
R
R
Donelli
G
G
D000199:Actins / Q000187:drug effects; D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000494:pharmacology*; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D016360:Clostridioides difficile; D004305:Dose-Response Relationship, Drug; D020558:GTP Phosphohydrolases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D007422:Intestines / Q000166:cytology / Q000187:drug effects*; D014176:Protein Biosynthesis; D051381:Rats; D020741:rho GTP-Binding Proteins
D000199:Actins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; C031815:toxB protein, Clostridium difficile; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020741:rho GTP-Binding Proteins