Cloning of Clostridium difficile toxin B gene and demonstration of high N-terminal homology between toxin A and B

Eichel‐Streiber, Christoph von; Laufenberg-Feldmann, R.; Sartingen, S; Schulze, Jürgen P.; Sauerborn, Markus

doi:10.1007/bf00192465

Cited by 45 publications

(14 citation statements)

References 15 publications

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“…The two well-characterized CBPs LytA and PspA contain within the C-terminal the repeated signature choline-binding domains that are the distinguishing feature of this family of proteins. As mentioned in the Introduction, these repeated domains have also been found in toxin A (Dove et al, 1990;Wren et al, 1990) and toxin B (Barroso et al, 1990;von Eichel-Streiber et al, 1990) of Clostridia spp. and the glucan-binding proteins and glucosyltransferases of other streptococci (Ferretti et al, 1987;Shiroza et al, 1987;Ueda et al, 1988;Banas et al, 1990;Gilmore et al, 1990).…”

Section: Discussionmentioning

confidence: 79%

Contribution of novel choline‐binding proteins to adherence, colonization and immunogenicity of Streptococcus pneumoniae

Rosenow

Ryan

Weiser

et al. 1997

Molecular Microbiology

437

465

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SummaryThe surface of Streptococcus pneumoniae is decorated with a family of choline-binding proteins (CBPs) that are non-covalently bound to the phosphorylcholine of the teichoic acid. Two examples (PspA, a protective antigen, and LytA, the major autolysin) have been well characterized. We identified additional CPBs and characterized a new CBP, CbpA, as an adhesin and a determinant of virulence. Using choline immobilized on a solid matrix, a mixture of proteins from a pspA-deficient strain of pneumococcus was eluted in a choline-dependent fashion. Antisera to these proteins passively protected mice challenged in the peritoneum with a lethal dose of pneumococci. The predominant component of this mixture, CbpA, is a 75-kDa surface-exposed protein that reacts with human convalescent antisera. The deduced sequence from the corresponding gene showed a chimeric architecture with a unique N-terminal region and a C-terminal domain consisting of 10 repeated choline-binding domains nearly identical to PspA. A cbpA-deficient mutant showed a >50% reduction in adherence to cytokine-activated human cells and failed to bind to immobilized sialic acid or lacto-N-neotetraose, known pneumococcal ligands on eukaryotic cells. Carriage of this mutant in an animal model of nasopharyngeal colonization was reduced 100-fold. There was no difference between the parent strain and this mutant in an intraperitoneal model of sepsis. These data for CbpA extend the important functions of the CBP family to bacterial adherence and identify a pneumococcal vaccine candidate.

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Section: Discussionmentioning

confidence: 79%

Contribution of novel choline‐binding proteins to adherence, colonization and immunogenicity of Streptococcus pneumoniae

Rosenow

Ryan

Weiser

et al. 1997

Molecular Microbiology

437

465

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“…Furthermore, the similarity in the biochemical activity of TcdA and TcdB, wherein both toxins use a highly conserved N-terminal domain to modify identical substrates, supports the notion of gene duplication. The major regions of homology between TcdA and TcdB fall within the enzymatic and receptor-binding domains of the two toxins (172). The N-terminal domains of TcdA and TcdB show 74% homology, and this homology provides a basis for the similar substrate specificity of these two toxins.…”

Section: Genetics Of Tcda and Tcdbmentioning

confidence: 99%

Clostridium difficileToxins: Mechanism of Action and Role in Disease

2005

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As the leading cause of hospital-acquired diarrhea, Clostridium difficile colonizes the large bowel of patients undergoing antibiotic therapy and produces two toxins, which cause notable disease pathologies. These two toxins, TcdA and TcdB, are encoded on a pathogenicity locus along with negative and positive regulators of their expression. Following expression and release from the bacterium, TcdA and TcdB translocate to the cytosol of target cells and inactivate small GTP-binding proteins, which include Rho, Rac, and Cdc42. Inactivation of these substrates occurs through monoglucosylation of a single reactive threonine, which lies within the effector-binding loop and coordinates a divalent cation critical to binding GTP. By glucosylating small GTPases, TcdA and TcdB cause actin condensation and cell rounding, which is followed by death of the cell. TcdA elicits effects primarily within the intestinal epithelium, while TcdB has a broader cell tropism. Important advances in the study of these toxins have been made in the past 15 years, and these are detailed in this review. The domains, subdomains, and residues of these toxins important for receptor binding and enzymatic activity have been elegantly studied and are highlighted herein. Furthermore, there have been major advances in defining the role of these toxins in modulating the inflammatory events involving the disruption of cell junctions, neuronal activation, cytokine production, and infiltration by polymorphonuclear cells. Collectively, the present review provides a comprehensive update on TcdA and TcdB's mechanism of action as well as the role of these toxins in disease

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“…More recently, von Eichel-Streiber et al (281,282) isolated cytotoxin B fragments from a C. difficile expression library by using C. sordellii lethal toxin antiserum. A partial restriction map of recombinant clones showed that the toxB gene is positioned upstream of utxA and toxA and has a size of 6.9 kb corresponding to a polypeptide size of 250 kDa.…”

Section: Introductionmentioning

confidence: 99%

Clostridium difficile: clinical disease and diagnosis

1993

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Clostridium difficile is an opportunistic pathogen that causes a spectrum of disease ranging from antibiotic-associated diarrhea to pseudomembranous colitis. Although the disease was first described in 1893, the etiologic agent was not isolated and identified until 1978. Since clinical and pathological features of C. difficile-associated disease are not easily distinguished from those of other gastrointestinal diseases, including ulcerative colitis, chronic inflammatory bowel disease, and Crohn's disease, diagnostic methods have relied on either isolation and identification of the microorganism or direct detection of bacterial antigens or toxins in stool specimens. The current review focuses on the sensitivity, specificity, and practical use of several diagnostic tests, including methods for culture of the etiologic agent, cellular cytotoxicity assays, latex agglutination tests, enzyme immunoassay systems, counterimmunoelectrophoresis, fluorescent-antibody assays, and polymerase chain reactions.

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Cloning of Clostridium difficile toxin B gene and demonstration of high N-terminal homology between toxin A and B

Cited by 45 publications

References 15 publications

Contribution of novel choline‐binding proteins to adherence, colonization and immunogenicity of Streptococcus pneumoniae

Contribution of novel choline‐binding proteins to adherence, colonization and immunogenicity of Streptococcus pneumoniae

Clostridium difficileToxins: Mechanism of Action and Role in Disease

Clostridium difficile: clinical disease and diagnosis

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