Evidence map›Paper›PMID 27680706›Full record

ArticleNature2016

Frizzled proteins are colonic epithelial receptors for C. difficile toxin B.

Liang Tao, Jie Zhang, Paul Meraner, Alessio Tovaglieri, Xiaoqian Wu, Ralf Gerhard, Xinjun Zhang, William B Stallcup, Ji Miao, Xi He and 4 more

Abstract read
In one paragraph

Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 172 papers.

0numbers the graph read from it
0cells of the map it votes in
172citing papers in PubMed
21.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

172 citing papers in PubMed, 263 citations in OpenAlex.

  1. Trial
  2. Article
  3. Article
  4. Review
  5. Article
  6. Monoclonal Antibodies Targeting Bacterial Infections: A Broad Review of the Field.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  7. Review
  8. Article
  9. CSPG4 Mediates Inflammatory, Cell Death, and Senescence Responses in Enteric Glia Exposed to Clostridioides difficile Toxins.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  10. Review
  11. Clostridioides difficile pathogenesis and control.Nature reviews. Microbiology · 2026
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Mouse monoclonal antibodies againstInfection and immunity · 2025
    Article
  18. Unravelling three-way interactions betweenJournal of medical microbiology · 2025
    Review
  19. Review
  20. Review

112 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 2 countries.

Liang TaoDepartment of Urology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Jie ZhangDepartment of Urology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Paul MeranerDepartment of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Alessio TovaglieriDivision of Endocrinology, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
Xiaoqian WuCenter for Infectious and Inflammatory Diseases, Texas A &M Health Science Center, Houston, Texas 77030, USA.
Ralf GerhardInstitute of Toxicology, Hannover Medical School, 30625 Hannover, Germany.
Xinjun ZhangThe F. M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
William B StallcupTumor Microenvironment and Cancer Immunology Program, Sanford-Burnham Prebys Medical Discovery Institute, Cancer Center, La Jolla, California 92037, USA.
Ji MiaoDivision of Endocrinology, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
Xi HeThe F. M. Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Julian G HurdleCenter for Infectious and Inflammatory Diseases, Texas A &M Health Science Center, Houston, Texas 77030, USA.
David T BreaultDivision of Endocrinology, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
Abraham L BrassDepartment of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Min DongDepartment of Urology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Harvard University · USUniversity of Massachusetts Chan Medical School · USBoston Children's Museum · USMedizinische Hochschule Hannover · DESanford Burnham Prebys Medical Discovery Institute · US

Funding

STRUCTURE-FUNCTION RELATIONSHIPS IN THE ALIMENTARY TRACTP30DK034854 · NIDDK · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JONATHAN C KAGAN · 1986 to 2026
$32.4M
SYNAPTIC MECHANISMS IN HIPPOCAMPAL EPILEPTOGENESISP30HD018655 · NICHD · CHILDREN'S HOSPITAL BOSTON · PI POMEROY, SCOTT LOREN · 1985 to 2015
$26.2M
Long-term effects of botulinum neurotoxins on neuronal viabilityR01NS080833 · NINDS · HARVARD MEDICAL SCHOOL · PI Min Dong · 2013 to 2026
$6.8M
Wnt-LRP interaction in Wnt signal transductionR01GM057603 · NIGMS · CHILDREN'S HOSPITAL BOSTON · PI HE, XI · 1999 to 2018
$6.3M
NG2-PG in tumor vascularization and progressionR01CA095287 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI STALLCUP, WILLIAM B. · 2002 to 2016
$5.3M
Genetic and Chemical Biological Studies of a Novel Wnt Inhibitor Tiki2R01AR060359 · NIAMS · BOSTON CHILDREN'S HOSPITAL · PI HE, XI · 2011 to 2015
$2.8M
Characterization of Telomerase Expressing Intestinal Stem CellsR01DK084056 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI BREAULT, DAVID T · 2010 to 2015
$2.2M
The Role of IFITM3 in the Anti-viral Host ResponseR01AI091786 · NIAID · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BRASS, ABRAHAM L · 2011 to 2015
$2.1M
Nature inspired treatments for persistent C. difficile infectionsR01AT006732 · NCCIH · UNIVERSITY OF TEXAS ARLINGTON · PI HURDLE, JULIAN G · 2011 to 2015
$1.9M
Insulin Regulation of Liver X Receptor in Normal and Insulin Resistant StatesR00DK100539 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI MIAO, JI · 2016 to 2018
$747k
Insulin Regulation of Liver X Receptor in Normal and Insulin Resistant StatesK99DK100539 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI MIAO, JI · 2013 to 2014
$180k
NCCIH NIH HHS R01 AT006732NCI NIH HHS R01 CA095287NIAID NIH HHS R01 AI091786NIAMS NIH HHS R01 AR060359NICHD NIH HHS P30 HD018655NIDDK NIH HHS K99 DK100539NIDDK NIH HHS P30 DK034854NIDDK NIH HHS R00 DK100539NIDDK NIH HHS R01 DK084056NIGMS NIH HHS R01 GM057603NINDS NIH HHS R01 NS080833
6 · The paper itself

Abstract

Clostridium difficile toxin B (TcdB) is a critical virulence factor that causes diseases associated with C. difficile infection. Here we carried out CRISPR-Cas9-mediated genome-wide screens and identified the members of the Wnt receptor frizzled family (FZDs) as TcdB receptors. TcdB binds to the conserved Wnt-binding site known as the cysteine-rich domain (CRD), with the highest affinity towards FZD1, 2 and 7. TcdB competes with Wnt for binding to FZDs, and its binding blocks Wnt signalling. FZD1/2/7 triple-knockout cells are highly resistant to TcdB, and recombinant FZD2-CRD prevented TcdB binding to the colonic epithelium. Colonic organoids cultured from FZD7-knockout mice, combined with knockdown of FZD1 and 2, showed increased resistance to TcdB. The colonic epithelium in FZD7-knockout mice was less susceptible to TcdB-induced tissue damage in vivo. These findings establish FZDs as physiologically relevant receptors for TcdB in the colonic epithelium.

Indexed as

AnimalsAntigensBacterial ProteinsBacterial ToxinsBinding SitesCell LineCHO CellsChondroitin Sulfate Proteoglycan 4Clostridioides difficileColonCricetulusCRISPR-Cas SystemsEpitheliumFemaleFrizzled ReceptorsGene Knockout TechniquesAntigensBacterial ProteinsBacterial ToxinsChondroitin Sulfate Proteoglycan 4Frizzled ReceptorsOligopeptidesProteoglycanstoxB protein, Clostridium difficileVirulence FactorsWnt Proteins

Identifiers

PMID27680706
PMCPMC5519134
OpenAlexW2525231178

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.