Evidence map›Paper›PMID 35272717›Full record

ArticleMicrobiome2022

A mouse model of occult intestinal colonization demonstrating antibiotic-induced outgrowth of carbapenem-resistant Enterobacteriaceae.

Choon K Sim, Sara Saheb Kashaf, Apollo Stacy, Diana M Proctor, Alexandre Almeida, Nicolas Bouladoux, Mark Chen, NISC Comparative Sequencing Program, Robert D Finn, Yasmine Belkaid and 2 more

Open access · goldAbstract readVideo-Audio Media
In one paragraph

Article in Microbiome, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

22 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Article
  3. Molecular Insights into Carbapenem Resistance inInternational journal of molecular sciences · 2026
    Review
  4. Article
  5. Sugar Import SuppressesbioRxiv : the preprint server for biology · 2025
    Article
  6. Article
  7. Article
  8. Diagnostics (Basel, Switzerland) · 2025
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Carbapenem-ResistantbioRxiv : the preprint server for biology · 2024
    Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Antibiotic perturbations to the gut microbiome.Nature reviews. Microbiology · 2023
    Review
  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

12 authors at 4 institutions in 3 countries.

Choon K SimMicrobial Genomics Section, Translational and Functional Genomics Branch, National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
Sara Saheb KashafMicrobial Genomics Section, Translational and Functional Genomics Branch, National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
Apollo StacyMetaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, 20892, USA.
Diana M ProctorMicrobial Genomics Section, Translational and Functional Genomics Branch, National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
Alexandre AlmeidaEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, UK.
Nicolas BouladouxMetaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, 20892, USA.
Mark ChenMicrobial Genomics Section, Translational and Functional Genomics Branch, National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, MD, 20892, USA.
NISC Comparative Sequencing Program
Robert D FinnEuropean Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton, UK.
Yasmine BelkaidMetaorganism Immunity Section, Laboratory of Host Immunity and Microbiome, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, 20892, USA.
Sean ConlanMicrobial Genomics Section, Translational and Functional Genomics Branch, National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, MD, 20892, USA. conlans@mail.nih.gov.
Julia A SegreMicrobial Genomics Section, Translational and Functional Genomics Branch, National Human Genome Research Institute (NHGRI), National Institutes of Health (NIH), Bethesda, MD, 20892, USA. jsegre@nhgri.nih.gov.ORCID 0000-0001-6860-348X
National Institutes of Health · USEuropean Bioinformatics Institute · GBAgency for Science, Technology and Research · SGNational Human Genome Research Institute · US

Funding

Inter- and Intra-Species Comparative SequencingZIBHG000196 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI THOMAS, JAMES · 2009 to 2025
$177.6M
Role of the microbiota in immunityZIAAI001115 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI BELKAID, YASMINE · 2009 to 2025
$22.4M
NIAID Microbiome ProgramZICAI001233 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI MOUTSOPOULOS, NIKI · 2018 to 2025
$18.9M
Microbial genomics of hospital-associated pathogensZIAHG200382 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI SEGRE, JULIA ANGELA · 2012 to 2025
$9.1M
6 · The paper itself

Abstract

backgroundThe human intestinal microbiome is a complex community that contributes to host health and disease. In addition to normal microbiota, pathogens like carbapenem-resistant Enterobacteriaceae may be asymptomatically present. When these bacteria are present at very low levels, they are often undetectable in hospital surveillance cultures, known as occult or subclinical colonization. Through the receipt of antibiotics, these subclinical pathogens can increase to sufficiently high levels to become detectable, in a process called outgrowth. However, little is known about the interaction between gut microbiota and Enterobacteriaceae during occult colonization and outgrowth.

resultsWe developed a clinically relevant mouse model for studying occult colonization. Conventional wild-type mice without antibiotic pre-treatment were exposed to Klebsiella pneumoniae but rapidly tested negative for colonization. This occult colonization was found to perturb the microbiome as detected by both 16S rRNA amplicon and shotgun metagenomic sequencing. Outgrowth of occult K. pneumoniae was induced either by a four-antibiotic cocktail or by individual receipt of ampicillin, vancomycin, or azithromycin, which all reduced overall microbial diversity. Notably, vancomycin was shown to trigger K. pneumoniae outgrowth in only a subset of exposed animals (outgrowth-susceptible). To identify factors that underlie outgrowth susceptibility, we analyzed microbiome-encoded gene functions and were able to classify outgrowth-susceptible microbiomes using pathways associated with mRNA stability. Lastly, an evolutionary approach illuminated the importance of xylose metabolism in K. pneumoniae colonization, supporting xylose abundance as a second susceptibility indicator. We showed that our model is generalizable to other pathogens, including carbapenem-resistant Escherichia coli and Enterobacter cloacae.

conclusionsOur modeling of occult colonization and outgrowth could help the development of strategies to mitigate the risk of subsequent infection and transmission in medical facilities and the wider community. This study suggests that microbiota mRNA and small-molecule metabolites may be used to predict outgrowth-susceptibility. Video Abstract.

Indexed as

Carbapenem-Resistant EnterobacteriaceaeAnimalsAnti-Bacterial AgentsIntestinesKlebsiella pneumoniaeMiceRNA, Ribosomal, 16SAnti-Bacterial AgentsRNA, Ribosomal, 16S16S rRNAAntibioticGutKlebsiellaMetagenomicMicrobiomemRNA stabilityOccultOutgrowthXylose

Identifiers

PMID35272717
PMCPMC8908617
OpenAlexW4221025768

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.