Evidence map›Paper›PMID 30418409›Full record

ArticleJournal of pediatric gastroenterology and nutrition2019

Bacteriophage Therapy Testing Against Shigella flexneri in a Novel Human Intestinal Organoid-Derived Infection Model.

Alejandro Llanos-Chea, Robert J Citorik, Kourtney P Nickerson, Laura Ingano, Gloria Serena, Stefania Senger, Timothy K Lu, Alessio Fasano, Christina S Faherty

Abstract read
In one paragraph

Article in Journal of pediatric gastroenterology and nutrition, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
–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

26 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Bacteriophage Therapy AgainstAntibiotics (Basel, Switzerland) · 2026
    Review
  4. Article
  5. Isolation and characterization of lyticFrontiers in cellular and infection microbiology · 2026
    Article
  6. Article
  7. Review
  8. Development of aApplied and environmental microbiology · 2024
    Article
  9. Review
  10. Review
  11. Review
  12. Functional assays to evaluate antibody-mediated responses againstFrontiers in cellular and infection microbiology · 2023
    Review
  13. Article
  14. Design of a Bacteriophage Cocktail Active againstAntibiotics (Basel, Switzerland) · 2022
    Article
  15. Article
  16. Article
  17. Evaluation of a Live AttenuatedPathogens (Basel, Switzerland) · 2021
    Article
  18. Article
  19. Article
  20. Review
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

9 authors.

Alejandro Llanos-CheaDivision of Pediatric Gastroenterology and Nutrition, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital.
Robert J CitorikMicrobiology Program.
Kourtney P NickersonDivision of Pediatric Gastroenterology and Nutrition, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital.
Laura InganoDivision of Pediatric Gastroenterology and Nutrition, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital.
Gloria SerenaDivision of Pediatric Gastroenterology and Nutrition, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital.
Stefania SengerDivision of Pediatric Gastroenterology and Nutrition, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital.
Timothy K LuMicrobiology Program.
Alessio FasanoDivision of Pediatric Gastroenterology and Nutrition, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital.
Christina S FahertyDivision of Pediatric Gastroenterology and Nutrition, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital.

Funding

Wild-type S. typhi Infection in Humans: Integrated Immunoprotective MechanismsU19AI082655 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI SZTEIN, MARCELO B. · 2009 to 2018
$27.8M
Interdepartmental Neuroscience CenterP30NS045776 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI BREAKEFIELD, XANDRA OWENS, TANNOUS, BAKHOS A · 2003 to 2018
$11.1M
MIT Center for Integrative Synthetic BiologyP50GM098792 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WEISS, RON · 2013 to 2017
$11.0M
Engineering “Phagebody” Antimicrobials for Carbapenem-Resistant EnterobacteriaceaeR33AI121669 · NIAID · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LU, TIMOTHY · 2018 to 2020
$1.3M
The mechanism of Shigella flexneri adherence during the early infection processK22AI104755 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI FAHERTY, CHRISTINA S · 2014 to 2015
$270k
Request for electron microscopeS10RR023594 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI DIFIGLIA, MARIAN · 2010 to 2010
$194k
NCRR NIH HHS S10 RR023594NIAID NIH HHS K22 AI104755NIAID NIH HHS R33 AI121669NIAID NIH HHS U19 AI082655NIGMS NIH HHS P50 GM098792NINDS NIH HHS P30 NS045776
6 · The paper itself

Abstract

objectiveEnteric bacterial pathogens cause diarrheal disease and mortality at significant rates throughout the world, particularly in children younger than 5 years. Our ability to combat bacterial pathogens has been hindered by antibiotic resistance, a lack of effective vaccines, and accurate models of infection. With the renewed interest in bacteriophage therapy, we sought to use a novel human intestinal model to investigate the efficacy of a newly isolated bacteriophage against Shigella flexneri.

methodsAn S. flexneri 2457T-specific bacteriophage was isolated and assessed through kill curve experiments and infection assays with colorectal adenocarcinoma HT-29 cells and a novel human intestinal organoid-derived epithelial monolayer model. In our treatment protocol, organoids were generated from intestinal crypt stem cells, expanded in culture, and seeded onto transwells to establish 2-dimensional monolayers that differentiate into intestinal cells.

resultsThe isolated bacteriophage efficiently killed S. flexneri 2457T, other S. flexneri strains, and a strain of 2457T harboring an antibiotic resistance cassette. Analyses with laboratory and commensal Escherichia coli strains demonstrated that the bacteriophage was specific to S. flexneri, as observed under co-culture conditions. Importantly, the bacteriophage prevented both S. flexneri 2457T epithelial cell adherence and invasion in both infection models.

conclusionsBacteriophages offer feasible alternatives to antibiotics for eliminating enteric pathogens, confirmed here by the bacteriophage-targeted killing of S. flexneri. Furthermore, application of the organoid model has provided important insight into Shigella pathogenesis and bacteriophage-dependent intervention strategies. The screening platform described herein provides proof-of-concept analysis for the development of novel bacteriophage therapies to target antibiotic-resistant pathogens.

Indexed as

Escherichia coliPhage TherapyShigella flexneriChildDiarrhea, InfantileFemaleHT29 CellsHumansInfantInfant, NewbornIntestinesMale

Identifiers

PMID30418409
PMCPMC6939622

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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.