Effects of Clostridium difficile toxins A and B on cytoskeleton organization in HEp-2 cells: a comparative morphological study.
A comparative study on the effects of toxin A and toxin B from Clostridium difficile on HEp-2 cells was carried out. Both toxins caused cell retraction and rounding and seemed to exert their effect on cell morphology via a rearrangement of actin and alpha-actinin microfilaments. Such a rearrangement occurred at an early stage, when no change in microtubular and cytokeratin systems was detectable. Nevertheless, several structural modifications accompanying the cytopathological process induced by toxins A and B appeared to be quite different. In particular, toxin B-treated cells showed an arborized phenotype as a result of cell retraction and rounding, whereas toxin A caused cell rounding without arborization. Moreover, nuclear polarization following disorganization of the microfilament system was only observed in toxin A-treated cells. The structural features distinguishing intoxication processes induced by the two toxins probably reflect a different mechanism of action and suggest the presence of a distinct subcellular component as a primary target for each toxin.
Fiorentini
C
C
Department of Ultrastructures, Istituto Superiore di Sanità, Rome, Italy.
Arancia
G
G
Paradisi
S
S
Donelli
G
G
Giuliano
M
M
Piemonte
F
F
Mastrantonio
P
P
D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D003013:Clostridium / Q000032:analysis; D003599:Cytoskeleton / Q000187:drug effects* / Q000648:ultrastructure; D004768:Enterotoxins; D004847:Epithelial Cells; D005455:Fluorescent Antibody Technique; D006801:Humans; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile