Evidence map›Paper›PMID 33513212›Full record

ArticlePLoS pathogens2021

A host receptor enables type 1 pilus-mediated pathogenesis of Escherichia coli pyelonephritis.

Lisa K McLellan, Michael R McAllaster, Arthur S Kim, Ľubomíra Tóthová, Patrick D Olson, Jerome S Pinkner, Allyssa L Daugherty, Teri N Hreha, James W Janetka, Daved H Fremont and 3 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
6.1field-weighted citation impact, top 3% 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

27 citing papers in PubMed, 42 citations in OpenAlex.

  1. Urinary tract infections in children.Nature reviews. Urology · 2026
    Review
  2. Article
  3. Review
  4. Article
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  6. Article
  7. Article
  8. LDL receptor-mediated endocytosis ofProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  9. Review
  10. Review
  11. Conformational ensembles inProceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  12. T3SS protein EsrC binds to theApplied and environmental microbiology · 2024
    Article
  13. Review
  14. Intercalated cell function, kidney innate immunity, and urinary tract infections.Pflugers Archiv : European journal of physiology · 2024
    Review
  15. Article
  16. Uropathogen and host responses in pyelonephritis.Nature reviews. Nephrology · 2023
    Review
  17. Immune defenses in the urinary tract.Trends in immunology · 2023
    Review
  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

13 authors at 1 institution in 1 country.

Lisa K McLellanDepartment of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, United States of America.ORCID 0000-0001-6418-8039
Michael R McAllasterDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.ORCID 0000-0001-9729-7290
Arthur S KimDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.ORCID 0000-0003-4101-6642
Ľubomíra TóthováDepartment of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, United States of America.ORCID 0000-0001-9162-4916
Patrick D OlsonDepartment of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Jerome S PinknerDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.ORCID 0000-0002-7389-7440
Allyssa L DaughertyDepartment of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, United States of America.ORCID 0000-0001-8428-0422
Teri N HrehaDepartment of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, United States of America.ORCID 0000-0002-0041-2000
James W JanetkaDepartment of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri, United States of America.
Daved H FremontDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.ORCID 0000-0002-8544-2689
Scott J HultgrenDepartment of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, United States of America.ORCID 0000-0001-8785-564X
Herbert W VirginDepartment of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, United States of America.ORCID 0000-0001-8580-7628
David A HunstadDepartment of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, United States of America.ORCID 0000-0002-9848-0975
Washington University in St. Louis · US

Funding

Washington University Center for Cellular ImagingP30CA091842 · NCI · WASHINGTON UNIVERSITY · PI AIMEE S JAMES · 2001 to 2026
$128.0M
PATHOGENIC FIBER FORMATION IN BACTERIA: STRUCTURAL BASISR01AI048689 · NIAID · WASHINGTON UNIVERSITY · PI HULTGREN, SCOTT J. · 2001 to 2020
$7.6M
Pathogenic Fiber Formation in Bacteria: Structural BasisR37AI048689 · NIAID · WASHINGTON UNIVERSITY · PI SCOTT J. HULTGREN · 2021 to 2026
$2.9M
Cellular and Molecular Basis of Sex Specificity in UTI PathogenesisR01DK126697 · NIDDK · WASHINGTON UNIVERSITY · PI EARL, ASHLEE MIRIAM, HUNSTAD, DAVID · 2020 to 2024
$2.5M
SMALL MOLECULE BACTERIAL LECTIN ANTAGONISTS FOR UTI TREATMENT AND PREVENTIONR01DK108840 · NIDDK · WASHINGTON UNIVERSITY · PI HULTGREN, SCOTT J., JANETKA, JAMES W · 2017 to 2020
$2.1M
ANDROGEN INFLUENCE ON UTI SUSCEPTIBILITY AND SEVERITYR01DK111541 · NIDDK · WASHINGTON UNIVERSITY · PI HUNSTAD, DAVID · 2018 to 2021
$1.4M
Anti-virulence FimH inhibitors for the treatment and prevention of UTIsR43AI106112 · NIAID · FIMBRION THERAPEUTICS, INC. · PI HANNAN, THOMAS JOSEPH · 2014 to 2015
$569k
NCI NIH HHS P30 CA091842NIAID NIH HHS R01 AI048689NIAID NIH HHS R37 AI048689NIAID NIH HHS R43 AI106112NIDDK NIH HHS R01 DK108840NIDDK NIH HHS R01 DK111541NIDDK NIH HHS R01 DK126697
6 · The paper itself

Abstract

Type 1 pili have long been considered the major virulence factor enabling colonization of the urinary bladder by uropathogenic Escherichia coli (UPEC). The molecular pathogenesis of pyelonephritis is less well characterized, due to previous limitations in preclinical modeling of kidney infection. Here, we demonstrate in a recently developed mouse model that beyond bladder infection, type 1 pili also are critical for establishment of ascending pyelonephritis. Bacterial mutants lacking the type 1 pilus adhesin (FimH) were unable to establish kidney infection in male C3H/HeN mice. We developed an in vitro model of FimH-dependent UPEC binding to renal collecting duct cells, and performed a CRISPR screen in these cells, identifying desmoglein-2 as a primary renal epithelial receptor for FimH. The mannosylated extracellular domain of human DSG2 bound directly to the lectin domain of FimH in vitro, and introduction of a mutation in the FimH mannose-binding pocket abolished binding to DSG2. In infected C3H/HeN mice, type 1-piliated UPEC and Dsg2 were co-localized within collecting ducts, and administration of mannoside FIM1033, a potent small-molecule inhibitor of FimH, significantly attenuated bacterial loads in pyelonephritis. Our results broaden the biological importance of FimH, specify the first renal FimH receptor, and indicate that FimH-targeted therapeutics will also have application in pyelonephritis.

Indexed as

Adhesins, Escherichia coliAnimalsDesmoglein 2EpitheliumEscherichia coliEscherichia coli InfectionsFemaleFimbriae, BacterialFimbriae ProteinsHumansMaleMiceMice, Inbred C3HPyelonephritisUrinary BladderVirulenceAdhesins, Escherichia coliDesmoglein 2Dsg2 protein, mouseFimbriae ProteinsfimH protein, E coli

Identifiers

PMID33513212
PMCPMC7875428
OpenAlexW3125955315

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.