A comparative biochemical, pharmacological and immunological study of Clostridium novyi alpha-toxin, C. difficile toxin B and C. sordellii lethal toxin.
The three clostridial cytotoxins, i.e. alpha-toxin of C. novyi (Tox alpha-nov), toxin B of C. difficile (ToxB-dif) and lethal toxin of C. sordellii (LT-sor) consist of single peptide chains of about 200,000 (Tox alpha-nov), 250,000 (LT-sor) and 275,000 (ToxB-dif) mol. wts. ToxB-dif and LT-sor but not Tox alpha-nov cross-reacted with rabbit polyclonal antibodies. Toxicity upon i.v. injection in mice was similar (LD50, 100 hr, 50-200 ng/kg) and was characterized by a slowly developing fluid loss into the interstitial space. When injected into the rat paw the toxins caused a delayed local edema lasting for days. In vitro the three toxins provoked a persistent retraction of endothelial cells cultured from pig pulmonary artery. ToxB-dif and Tox alpha-nov triggered the accumulation of F-actin in the perinuclear region at the expense of the tight peripheral bands whereas LT-sor led to a random loss of microfilament structure. The toxins inhibited uridine incorporation into endothelial or chicken embryonic cells whereas T 84 cells responded by an about 10-fold increase of uridine incorporation. Neither toxin ADP-ribosylated actin. The similarities between the three cytotoxins warrant their arrangement into a common group which perturbs the microfilament system.
Bette
P
P
Rudolf-Buchheim-Institut für Pharmakologie, Justus-Liebig-Universität, F.R.G.
Oksche
A
A
Mauler
F
F
von Eichel-Streiber
C
C
Popoff
M R
MR
Habermann
E
E
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000276:immunology / Q000633:toxicity*; D002478:Cells, Cultured; D002642:Chick Embryo; D016360:Clostridioides difficile; D003013:Clostridium; D003603:Cytotoxins / Q000276:immunology / Q000633:toxicity*; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D007928:Lethal Dose 50; D051379:Mice; D008858:Microscopy, Phase-Contrast; D011188:Potassium / Q000378:metabolism; D011651:Pulmonary Artery; D051381:Rats; D011919:Rats, Inbred Strains; D014529:Uridine / Q000037:antagonists & inhibitors / Q000378:metabolism
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003603:Cytotoxins; C031815:toxB protein, Clostridium difficile; D000246:Adenosine Diphosphate Ribose; D011188:Potassium; D014529:Uridine