Variant toxin B and a functional toxin A produced by Clostridium difficile C34.
A particular property of Clostridium difficile strain C34 is an insertion of approximately 2 kb in the tcdA-C34 gene that does not hinder expression of a fully active TcdA-C34 molecule. Intoxication with TcdA-C34 induced an arborized appearance in eukaryotic cells (D-type cytopathic effect); intoxication with TcdB-C34 induced a spindle-like appearance of cells (S-type cytopathic effect). Inactivation of GTPases with purified toxins revealed that Rho, Rac, Cdc42, and Rap are substrates of TcdA-C34. The variant cytotoxin TcdB-C34 inactivated Rho, Rac, Cdc42, Rap, Ral, and R-Ras. Hence, this is the first 'S-type' cytotoxin which inactivates both Rho and R-Ras, and is coexpressed with a 'D-type' enterotoxin. Our results support the hypothesis that R-Ras is a key GTPase related to the S-type cytopathic effect and suggest that induction of a S-type cytopathic effect dominates induction of the D-type cytopathic effect.
Mehlig
M
M
Verfügungsgebäude für Forschung und Entwicklung, Institut für Medizinische Mikrobiologie und Hygiene, Johannes Gutenberg-Universität, Mainz, Germany.
Moos
M
M
Braun
V
V
Kalt
B
B
Mahony
D E
DE
von Eichel-Streiber
C
C
D000818:Animals; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000235:genetics* / Q000633:toxicity; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D016360:Clostridioides difficile / Q000235:genetics* / Q000472:pathogenicity; D006224:Cricetinae; D003603:Cytotoxins / Q000235:genetics / Q000633:toxicity; D004251:DNA Transposable Elements; D004768:Enterotoxins / Q000235:genetics* / Q000633:toxicity; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D012867:Skin / Q000166:cytology / Q000187:drug effects* / Q000648:ultrastructure
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003603:Cytotoxins; D004251:DNA Transposable Elements; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile