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We began analyzing https://www.nature.com/articles/cr2014169, but it redirected us to https://www.nature.com/articles/cr2014169. The analysis below is for the second page.

Title[redir]:
Chondroitin sulfate proteoglycan 4 functions as the cellular receptor for Clostridium difficile toxin B | Cell Research
Description:
As a gram-positive, spore-forming anaerobic bacillus, Clostridium difficile (C. difficile) is responsible for severe and fatal pseudomembranous colitis, and poses the most urgent antibiotic resistance threat worldwide. Epidemic C. difficile is the leading cause of antibiotic-associated diarrhoea globally, especially diarrhoea due to the emergence of hypervirulent strains associated with high mortality and morbidity. TcdB, one of the key virulence factors secreted by this bacterium, enters host cells through a poorly understood mechanism to elicit its pathogenic effect. Here we report the first identification of the TcdB cellular receptor, chondroitin sulfate proteoglycan 4 (CSPG4). CSPG4 was initially isolated from a whole-genome human shRNAmir library screening, and its role was confirmed by both TALEN- and CRISPR/Cas9-mediated gene knockout in human cells. CSPG4 is critical for TcdB binding to the cell surface, inducing cytoskeleton disruption and cell death. A direct interaction between the N-terminus of CSPG4 and the C-terminus of TcdB was confirmed, and the soluble peptide of the toxin-binding domain of CSPG4 could protect cells from the action of TcdB. Notably, the complete loss of CSPG4/NG2 decreased TcdB-triggered interleukin-8 induction in mice without significantly affecting animal mortality. Based on both the in vitro and in vivo studies, we propose a dual-receptor model for TcdB endocytosis. The discovery of the first TcdB receptor reveals a previously unsuspected role for CSPG4 and provides a new therapeutic target for the treatment of C. difficile infection.

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Keywords {🔍}

tcdb, cells, cspg, cell, article, figure, toxin, google, scholar, cas, protein, difficile, domain, analysis, information, receptor, hela, clostridium, nature, human, supplementary, binding, rac, proteoglycan, library, surface, proteins, cspgn, assay, mice, effect, data, gene, rounding, chondroitin, expression, wildtype, research, toxicity, mouse, sulfate, interaction, tcda, helacspg, incubated, cellular, endocytosis, time, immunoblotting, glucosylation,

Topics {✒️}

nature portfolio alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid privacy policy gregorio perez-cordon & hanping feng advertising open reading frame anti-angiogenic therapy social media cell research website goat anti-human igg author information authors plant gene research 0 reprints nature 2009 nature 2010 nature 1995 nature 2014 nature 2001 nature crispr/cas9-mediated gene knockout tcdb-caused cell-rounding phenotype exhibits mono-glucosyltransferase activity4 dedicated pathogen-free facilities creative commons attribution-noncommercial mouse anti-human igg alexa-fluor 488-labelled tcdb multi-domain schematic diagram original library cells author correspondence human mucosa/submucosa interactions spore-forming anaerobic bacillus nucleotide sugar udp-glucose targeted genes laminin g-type motifs research route n-terminal glucosyltransferase domain poly-l-lysine coverslips membrane-spanning proteoglycan ng2 epithelial cell necrosis clostridioides difficile toxin toxin-induced cell rounding full-length cspg4 protein putative receptor-binding domain tcdb-induced cell death kaplan-meier survival curves vis-a-vis significance laminin g-type domains single-chain proteins possessing tcdb-induced cell rounding high molecular weight-melanoma

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      headline:Chondroitin sulfate proteoglycan 4 functions as the cellular receptor for Clostridium difficile toxin B
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      name:Tuxiong Huang
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            name:University of Maryland Dental School
            address:
               name:Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, USA
               type:PostalAddress
            type:Organization
      name:Gregorio Perez-Cordon
      affiliation:
            name:University of Maryland Dental School
            address:
               name:Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, USA
               type:PostalAddress
            type:Organization
      name:Hanping Feng
      affiliation:
            name:University of Maryland Dental School
            address:
               name:Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, USA
               type:PostalAddress
            type:Organization
      name:Wensheng Wei
      affiliation:
            name:Biodynamic Optical Imaging Center (BIOPIC), State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University
            address:
               name:Biodynamic Optical Imaging Center (BIOPIC), State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Biodynamic Optical Imaging Center (BIOPIC), State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China
      name:Biodynamic Optical Imaging Center (BIOPIC), State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China
      name:Biodynamic Optical Imaging Center (BIOPIC), State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China
      name:Biodynamic Optical Imaging Center (BIOPIC), State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China
      name:Biodynamic Optical Imaging Center (BIOPIC), State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China
      name:Biodynamic Optical Imaging Center (BIOPIC), State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China
      name:Biodynamic Optical Imaging Center (BIOPIC), State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China
      name:Biodynamic Optical Imaging Center (BIOPIC), State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China
      name:Biodynamic Optical Imaging Center (BIOPIC), State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China
      name:School of Bioscience and Biotechnology, South China University of Technology, Guangzhou, China
      name:Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, USA
      name:Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, USA
      name:Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, USA
      name:Biodynamic Optical Imaging Center (BIOPIC), State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China

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