Evidence map›Paper›PMID 27780864›Full record

ArticleThe Journal of biological chemistry2016

Human Metabolome-derived Cofactors Are Required for the Antibacterial Activity of Siderocalin in Urine.

Robin R Shields-Cutler, Jan R Crowley, Connelly D Miller, Ann E Stapleton, Weidong Cui, Jeffrey P Henderson

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
–field-weighted citation impact
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

24 citing papers in PubMed.

  1. Article
  2. In defence of ferroptosis.Signal transduction and targeted therapy · 2025
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. UropathogenicbioRxiv : the preprint server for biology · 2023
    Article
  9. Review
  10. Article
  11. ThemBio · 2022
    Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. The Underlying Molecular Mechanisms Involved in Traditional Chinese MedicineEvidence-based complementary and alternative medicine : eCAM · 2021
    Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Robin R Shields-CutlerFrom the Division of Infectious Diseases, Department of Medicine.
Jan R Crowleythe Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Connelly D MillerFrom the Division of Infectious Diseases, Department of Medicine.
Ann E Stapletonthe Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington 98195, and.
Weidong Cuithe Department of Chemistry, Washington University, St. Louis, Missouri 63130.
Jeffrey P HendersonFrom the Division of Infectious Diseases, Department of Medicine, jhenderson@DOM.wustl.edu.

Funding

Washington University Institute of Clinical and Translational SciencesUL1TR000448 · NCATS · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2012 to 2016
$41.4M
Washington University Nutrition Obesity Research CenterP30DK056341 · NIDDK · WASHINGTON UNIVERSITY · PI Dominic N Reeds · 1999 to 2026
$30.2M
WU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI Clay F. Semenkovich · 2013 to 2026
$27.1M
pan-Genome of E.coli in the bladder and gut of women with recurrent UTIP50DK064540 · NIDDK · WASHINGTON UNIVERSITY · PI HULTGREN, SCOTT J. · 2002 to 2017
$17.9M
YOGA LIFESTYLE INTERVENTION REDUCES BLOOD PRESSURE IN HIV-INFECTED ADULTSP41RR000954 · NCRR · WASHINGTON UNIVERSITY · PI TAYLOR, JOHN-STEPHEN ADOLFINO · 1985 to 2011
$16.0M
TrainingP41GM103422 · NIGMS · WASHINGTON UNIVERSITY · PI YARASHESKI, KEVIN E · 2012 to 2019
$12.0M
Lactobacillus probiotic for prevention of recurrent UTIR01DK088830 · NIDDK · UNIVERSITY OF WASHINGTON · PI STAPLETON, ANN E · 2011 to 2015
$3.0M
EXPRESSION AND IRON-INDEPENDENT FUNCTIONS OF SIDEROPHORES IN URINARY TRACT INFECTR01DK099534 · NIDDK · WASHINGTON UNIVERSITY · PI HENDERSON, JEFFREY P · 2014 to 2018
$1.8M
Metabolomic Mechanisms of Nutritional Immunity in the Urinary TractR56DK111930 · NIDDK · WASHINGTON UNIVERSITY · PI HENDERSON, JEFFREY P · 2016 to 2016
$125k
NCATS NIH HHS UL1 TR000448NCRR NIH HHS P41 RR000954NIDDK NIH HHS P30 DK020579NIDDK NIH HHS P30 DK056341NIDDK NIH HHS P50 DK064540NIDDK NIH HHS R01 DK088830NIDDK NIH HHS R01 DK099534NIDDK NIH HHS R56 DK111930NIGMS NIH HHS P41 GM103422
6 · The paper itself

Abstract

In human urinary tract infections, host cells release the antimicrobial protein siderocalin (SCN; also known as lipocalin-2, neutrophil gelatinase-associated lipocalin, or 24p3) into the urinary tract. By binding to ferric catechol complexes, SCN can sequester iron, a growth-limiting nutrient for most bacterial pathogens. Recent evidence links the antibacterial activity of SCN in human urine to iron sequestration and metabolomic variation between individuals. To determine whether these metabolomic associations correspond to functional Fe(III)-binding SCN ligands, we devised a biophysical protein binding screen to identify SCN ligands through direct analysis of human urine. This screen revealed a series of physiologic unconjugated urinary catechols that were able to function as SCN ligands of which pyrogallol in particular was positively associated with high urinary SCN activity. In a purified, defined culture system, these physiologic SCN ligands were sufficient to activate SCN antibacterial activity against Escherichia coli In the presence of multiple SCN ligands, native mass spectrometry demonstrated that SCN may preferentially combine different ligands to coordinate iron, suggesting that availability of specific ligand combinations affects in vivo SCN antibacterial activity. These results support a mechanistic link between the human urinary metabolome and innate immune function.

Indexed as

Escherichia coliAdolescentAdultAnti-Bacterial AgentsCarrier ProteinsCatecholsEscherichia coli InfectionsFemaleHumansImmunity, InnateLipocalin-2MetabolomeMiddle AgedUrinary Tract InfectionsAnti-Bacterial AgentsCarrier ProteinsCatecholsLCN2 protein, humanLipocalin-2Escherichia coli (E. coli)host-pathogen interactioninfectious diseaseironlipocalin 2mass spectrometry (MS)NGALsiderocalinsiderophoreurinary tract infection

Identifiers

PMID27780864
PMCPMC5207064

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Registered trials

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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.