Repetitive domain of Clostridium difficile toxin B exhibits cytotoxic effects on human intestinal epithelial cells and decreases epithelial barrier function.
We have used recombinant repetitive domain of Clostridium difficile toxin B obtained from two different strains, rec-TcdB3(10463) and rec-TcdB3(8864) and a model intestinal epithelial cell line(s) to characterize their cytotoxic and cytopathic effect and influence on tight-junction organization. Both recombinant receptor binding domains caused intestinal epithelial cell damage, decreased transepithelial electrical resistance and induced translocation of ZO-1 from tight-junction proteins although less efficiently as holotoxins. Recombinant repetitive TcdB domains also caused stimulation of interleukin IL-8 synthesis in HT-29 cells. This is the first description of glucosyltransferase independent toxicity of TcdB and these C-terminal mediated effects may contribute to the pathophysiology of C. difficile infection.
Zemljic
Mateja
M
Institute of Public Health Maribor, Centre for Microbiology, Research Department, Maribor, Slovenia.
Rupnik
Maja
M
Scarpa
Melania
M
Anderluh
Gregor
G
Palù
Gorgio
G
Castagliuolo
Ignazio
I
D001426:Bacterial Proteins / Q000633:toxicity*; D001427:Bacterial Toxins / Q000633:toxicity*; D016360:Clostridioides difficile / Q000472:pathogenicity*; D004768:Enterotoxins / Q000494:pharmacology / Q000633:toxicity*; D004847:Epithelial Cells / Q000382:microbiology*; D005964:Glucosyltransferases / Q000378:metabolism / Q000633:toxicity; D019073:HT29 Cells; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D054730:Protein Interaction Domains and Motifs; D019108:Tight Junctions
D001426:Bacterial Proteins; D001427:Bacterial Toxins; C508606:CXCL8 protein, human; D004768:Enterotoxins; D016209:Interleukin-8; C031815:toxB protein, Clostridium difficile; D005964:Glucosyltransferases