Rabbit sucrase-isomaltase contains a functional intestinal receptor for Clostridium difficile toxin A.

Pothoulakis, C; Gilbert, Russell; Cladaras, Christos; Castagliuolo, Ignazio; Semenza, Giorgio; Hitti, Youssef; Montcrief, J S; Linevsky, Joanne K.; Kelly, Ciarán P.; Nikulásson, Sigfús; Desai, Hema; Wilkins, Tracy D.; LaMont, J. Thomas

doi:10.1172/jci118835

Cited by 100 publications

(87 citation statements)

References 56 publications

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“…difficile toxin A, like other ADP-ribosylating toxins, must bind to intestinal epithelial cells in vivo to exert its adjuvant activity. It is possible that the differences in the immune responses elicited by CT, EtxB, and TxA C314 are due, at least in part, to different properties for binding to the gastrointestinal and nasopharyngeal mucosa (39,46). Indeed, the sugar binding properties can confine lectins to specific cell populations, such as M cells in the Peyer's patches or the follicle-associated epithelium in nasopharyngeal tissue (5,24).…”

Section: Discussionmentioning

confidence: 99%

Clostridium difficileToxin A Carboxyl-Terminus Peptide Lacking ADP-Ribosyltransferase Activity Acts as a Mucosal Adjuvant

et al. 2004

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The receptor binding domains of the most potent mucosal adjuvants, bacterial toxins and plant lectins, are organized in repeat units to recognize specific sugar residues. The lectin-like structure of the C-terminal region of Clostridium difficile toxin A prompted us to investigate the mucosal adjuvant properties of a nontoxigenic peptide corresponding to amino acids 2394 to 2706 (TxA C314 ). We compared TxA C314 adjuvant activity to those of cholera toxin (

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Section: Discussionmentioning

confidence: 99%

Clostridium difficileToxin A Carboxyl-Terminus Peptide Lacking ADP-Ribosyltransferase Activity Acts as a Mucosal Adjuvant

et al. 2004

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“…Toxin A binds to a G protein-coupled receptor (11) on the luminal aspect of the apical intestinal epithelial cell membrane (12) and is then internalized where it activates MAPKs 1 (13), intracellular calcium release (14,15), release of reactive oxygen species (ROS) (12,16), and secretion of pro-inflammatory mediators (16,17). We previously reported that toxin A releases prostaglandin E 2 (PGE 2 ) into the ileal lumen of intact rats (5) and Alcantara et al (18) reported that toxin A-induced water and electrolyte secretion in vivo was significantly blocked by a COX-2 inhibitor.…”

mentioning

confidence: 99%

Clostridium difficile Toxin A Regulates Inducible Cyclooxygenase-2 and Prostaglandin E2 Synthesis in Colonocytes via Reactive Oxygen Species and Activation of p38 MAPK

Kim

Rhee

Kokkotou

et al. 2005

Journal of Biological Chemistry

118

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“…It has been suggested that these toxins are constructed of three functional parts (18). The C terminus, which consists of a large region of repetitive oligopeptides, is assumed to be important for receptor binding to the eukaryotic target (19). A hydrophobic region almost in the middle of the toxins is believed to participate in membrane translocation, and finally, the N terminus harbors the enzyme activity.…”

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confidence: 99%

A Common Motif of Eukaryotic Glycosyltransferases Is Essential for the Enzyme Activity of Large Clostridial Cytotoxins

Busch¹,

Hofmann²,

Selzer³

et al. 1998

Journal of Biological Chemistry

214

181

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A fragment of the N-terminal 546 amino acid residues of Clostridium sordellii lethal toxin possesses full enzyme activity and glucosylates Rho and Ras GTPases in vitro. Here we identified several amino acid residues in C. sordellii lethal toxin that are essential for the enzyme activity of the active toxin fragment. Exchange of aspartic acid at position 286 or 288 with alanine or asparagine decreased glucosyltransferase activity by about 5000-fold and completely blocked glucohydrolase activity. No enzyme activity was detected with the double mutant D286A/D288A. Whereas the wild-type fragment of C. sordellii lethal toxin was labeled by azido-UDP-glucose after UV irradiation, mutation of the DXD motif prevented radiolabeling. At high concentrations (10 mM) of manganese ions, the transferase activities of the D286A and D288A mutants but not that of wild-type fragment were increased by about 20-fold. The exchange of Asp 270 and Arg 273 reduced glucosyltransferase activity by about 200-fold and blocked glucohydrolase activity. The data indicate that the DXD motif, which is highly conserved in all large clostridial cytotoxins and also in a large number of glycosyltransferases, is functionally essential for the enzyme activity of the toxins and may participate in coordination of the divalent cation and/or in the binding of UDP-glucose.

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Rabbit sucrase-isomaltase contains a functional intestinal receptor for Clostridium difficile toxin A.

Abstract: The intestinal effects of Clostridium difficile toxin A are initiated by toxin binding to luminal enterocyte receptors. We reported previously that the rabbit ileal brush border (

Cited by 100 publications

References 56 publications

Clostridium difficileToxin A Carboxyl-Terminus Peptide Lacking ADP-Ribosyltransferase Activity Acts as a Mucosal Adjuvant

Clostridium difficileToxin A Carboxyl-Terminus Peptide Lacking ADP-Ribosyltransferase Activity Acts as a Mucosal Adjuvant

Clostridium difficile Toxin A Regulates Inducible Cyclooxygenase-2 and Prostaglandin E2 Synthesis in Colonocytes via Reactive Oxygen Species and Activation of p38 MAPK

A Common Motif of Eukaryotic Glycosyltransferases Is Essential for the Enzyme Activity of Large Clostridial Cytotoxins

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