Anti-C. difficile Toxin B Monoclonal antibody, Clone 6267

Clostridium difficile infection is the most common cause of antibiotic-associated diarrhea in developed countries. The major virulence factor, C. difficile toxin B (TcdB), targets colonic epithelia by binding to the frizzled (FZD) family of Wnt receptors, but how TcdB recognizes FZDs is unclear. Here, we present the crystal structure of a TcdB fragment in complex with the cysteine-rich domain of human FZD2 at 2.5-angstrom resolution, which reveals an endogenous FZD-bound fatty acid acting as a co-receptor for TcdB binding. This lipid occupies the binding site for Wnt-adducted palmitoleic acid in FZDs. TcdB binding locks the lipid in place, preventing Wnt from engaging FZDs and signaling. Our findings establish a central role of fatty acids in FZD-mediated TcdB pathogenesis and suggest strategies to modulate Wnt signaling.

Most of the studies showed that inflammatory bowel diseases (IBD) patients inflammatory bowel diseases with Clostridium difficile infection (CDI) have more of the whole range of short-and long-term worst outcomes than those without CDI. Initial infection with the BI/NAP1/027 epidemic clone was found to be a significant risk factor for relapse. However, current literature is suggesting increasingly that for patients with infections that fail to resolve with traditional antibiotic regimens, FMT's average cure rate of > 90%. We report a case of a 40-year-old man, diagnosed with ulcerative colitis (UC) in 2012 who presented in our clinic for 20 watery stools per day with mucus and blood, hypogastric pain, pyrexia and chills. Rectosigmoidoscopy and histopathological examination diagnosed active lesions of ulcerative colitis with Clostridium difficile (C. difficile) toxins A/B enzyme immunoassays (EIA) testing initially negative. The patient was non-responder at day 10 of intravenous (iv) corticotherapy and received induction therapy with Infliximab 5mg/kg. EIA testing for C. difficile was repeated at day 12 of hospitalization with positive results for toxins A/B, and associated oral therapy with vancomycin and metronidazole was initiated without clinical response in day 7, reasons for what intravenously therapy with tigeciclyne was started with good response. Patient was discharged after 10 days of tigeciclyne, but came back twice for two relapses of C. difficile colitis treated successfully with tigeciclyne, reasons for what fecal transplantation was performed in Matei Bals Institute in Bucharest which induced remission of both CDI and UC.