title: Glucosyltransferase activity of Clostridium difficile Toxin B is essential for disease pathogenesis.
abstract: Clostridium difficile TcdB harbors a glucosyltransferase that targets host Rho GTPases. However, the role of the enzyme activity in the induction of host intestinal disease has not been demonstrated. In this study, we established a mouse acute intestinal disease model by cecum injection of wild type and glucosyltransferase-deficient TcdB and a chronic model by delivering toxin intraluminally via engineered surrogate host Bacillus megaterium. We demonstrated, for the first time, that the glucosyltransferase activity of TcdB is essential for inducing disease symptoms and intestinal pathological responses that resemble human disease, highlighting the importance of targeting toxin glucosyltransferase activity for future therapy.
authors.affiliation: a Department of Microbial Pathogenesis ; University of Maryland Dental School ; Baltimore , MD USA.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yang
authors.forename: Yongrong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Tuxiong
authors.initials: T
authors.lastname: Huang
authors.forename: Hanping
authors.initials: H
authors.lastname: Feng
mesh_terms: D000818:Animals; D001410:Bacillus megaterium / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity*; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity*; D001835:Body Weight; D002432:Cecum / Q000473:pathology; D003015:Clostridium Infections / Q000473:pathology*; D004195:Disease Models, Animal; D005964:Glucosyltransferases / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity*; D006651:Histocytochemistry; D007422:Intestines / Q000473:pathology; D051379:Mice; D008853:Microscopy; D016019:Survival Analysis
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; C031815:toxB protein, Clostridium difficile; D005964:Glucosyltransferases
keywords: Clostridium difficile; glucosyltransferase; pathogenesis; toxin