Evidence map›Paper›PMID 29112397›Full record

ArticleJournal of the American Chemical Society2017

ClbS Is a Cyclopropane Hydrolase That Confers Colibactin Resistance.

Prabhanshu Tripathi, Emilee E Shine, Alan R Healy, Chung Sub Kim, Seth B Herzon, Steven D Bruner, Jason M Crawford

Open access · greenAbstract read
In one paragraph

Article in Journal of the American Chemical Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
5.7field-weighted citation impact, top 4% 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

44 citing papers in PubMed, 78 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Harnessing the microbiome for cancer therapy.Nature reviews. Microbiology · 2026
    Review
  5. Microbiome-Genome Crosstalk in Colorectal Cancer: Colibactin Signatures andInternational journal of molecular sciences · 2026
    Review
  6. Article
  7. Article
  8. Article
  9. Emerging antibiotic resistance by various novel proteins/enzymes.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025
    Review
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Current understandings of colibactin regulation.Microbiology (Reading, England) · 2024
    Review
  16. Article
  17. Review
  18. Targeted depletion ofmSystems · 2023
    Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

Prabhanshu TripathiDepartment of Chemistry, University of Florida , Gainesville, Florida 32611, United States.ORCID 0000-0003-1282-2848
Emilee E ShineDepartment of Microbial Pathogenesis, Yale School of Medicine , New Haven, Connecticut 06536, United States.
Alan R HealyChemical Biology Institute, Yale University , West Haven, Connecticut 06516, United States.ORCID 0000-0002-1231-8353
Chung Sub KimChemical Biology Institute, Yale University , West Haven, Connecticut 06516, United States.
Seth B HerzonDepartment of Chemistry, Yale University , New Haven, Connecticut 06520, United States.ORCID 0000-0001-5940-9853
Steven D BrunerDepartment of Chemistry, University of Florida , Gainesville, Florida 32611, United States.ORCID 0000-0002-0522-480X
Jason M CrawfordDepartment of Microbial Pathogenesis, Yale School of Medicine , New Haven, Connecticut 06536, United States.ORCID 0000-0002-7583-1242
Yale University · USUniversity of Florida · US

Funding

Cryptic gut bacterial metabolites that regulate colorectal cancer formationDP2CA186575 · NCI · YALE UNIVERSITY · PI CRAWFORD, JASON MICHAEL · 2013 to 2013
$2.5M
Synthesis and Study of Complex Antiproliferative and Antimalarial Natural ProductsR01GM110506 · NIGMS · YALE UNIVERSITY · PI HERZON, SETH B. · 2015 to 2018
$1.2M
NCI NIH HHS DP2 CA186575NIGMS NIH HHS R01 GM110506
6 · The paper itself

Abstract

Certain commensal Escherichia coli contain the clb biosynthetic gene cluster that codes for small molecule prodrugs known as precolibactins. Precolibactins are converted to colibactins by N-deacylation; the latter are postulated to be genotoxic and to contribute to colorectal cancer formation. Though advances toward elucidating (pre)colibactin biosynthesis have been made, the functions and mechanisms of several clb gene products remain poorly understood. Here we report the 2.1 Å X-ray structure and molecular function of ClbS, a gene product that confers resistance to colibactin toxicity in host bacteria and which has been shown to be important for bacterial viability. The structure harbors a potential colibactin binding site and shares similarity to known hydrolases. In vitro studies using a synthetic colibactin analog and ClbS or an active site residue mutant reveal cyclopropane hydrolase activity that converts the electrophilic cyclopropane of the colibactins into an innocuous hydrolysis product. As the cyclopropane has been shown to be essential for genotoxic effects in vitro, this ClbS-catalyzed ring-opening provides a means for the bacteria to circumvent self-induced genotoxicity. Our study provides a molecular-level view of the first reported cyclopropane hydrolase and support for a specific mechanistic role of this enzyme in colibactin resistance.

Indexed as

Drug ResistanceBinding SitesCrystallography, X-RayCyclopropanesEscherichia coliHydrolasesMicrobial ViabilityPeptidesPolyketidescolibactinCyclopropanesHydrolasesPeptidesPolyketides

Identifiers

PMID29112397
PMCPMC6202678
OpenAlexW2767541325

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.