Evidence map›Paper›PMID 39556591›Full record

ArticlePLoS biology2024

Niche-specific metabolic phenotypes can be used to identify antimicrobial targets in pathogens.

Emma M Glass, Lillian R Dillard, Glynis L Kolling, Andrew S Warren, Jason A Papin

Abstract read
In one paragraph

Article in PLoS biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Environmental formermSystems · 2026
    Article
  2. Article
  3. Review
  4. Anti-infective compounds forSustainable microbiology · 2026
    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

5 authors.

Emma M GlassDepartment of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, United States of America.ORCID 0000-0002-7207-0011
Lillian R DillardDepartment of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, United States of America.
Glynis L KollingDepartment of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, United States of America.
Andrew S WarrenBiocomplexity Institute and Initiative, University of Virginia, Charlottesville, Virginia, United States of America.
Jason A PapinDepartment of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, United States of America.ORCID 0000-0002-2769-5805

Funding

Biotechnology Training ProgramT32GM136615 · NIGMS · UNIVERSITY OF VIRGINIA · PI Silvia Salinas Blemker, Kimberly A. Kelly · 2020 to 2026
$3.4M
Multi-scale model of microbial phenotype modulation by mucinsR01AI154242 · NIAID · UNIVERSITY OF VIRGINIA · PI FORD, ROSEANNE, PAPIN, JASON · 2020 to 2024
$3.1M
Systems biology of microbe-mediated glucosinolate bioconversion in inflammatory bowel diseaseR01AT010253 · NCCIH · UNIVERSITY OF VIRGINIA · PI PAPIN, JASON · 2018 to 2021
$2.0M
Interdisciplinary Training in Systems & Biomolecular Data ScienceT32GM145443 · NIGMS · UNIVERSITY OF VIRGINIA · PI Kevin A Janes, Jason Papin · 2022 to 2026
$1.5M
NCCIH NIH HHS R01 AT010253NIAID NIH HHS R01 AI154242NIGMS NIH HHS T32 GM136615NIGMS NIH HHS T32 GM145443
6 · The paper itself

Abstract

Bacterial pathogens pose a major risk to human health, leading to tens of millions of deaths annually and significant global economic losses. While bacterial infections are typically treated with antibiotic regimens, there has been a rapid emergence of antimicrobial resistant (AMR) bacterial strains due to antibiotic overuse. Because of this, treatment of infections with traditional antimicrobials has become increasingly difficult, necessitating the development of innovative approaches for deeply understanding pathogen function. To combat issues presented by broad- spectrum antibiotics, the idea of narrow-spectrum antibiotics has been previously proposed and explored. Rather than interrupting universal bacterial cellular processes, narrow-spectrum antibiotics work by targeting specific functions or essential genes in certain species or subgroups of bacteria. Here, we generate a collection of genome-scale metabolic network reconstructions (GENREs) of pathogens through an automated computational pipeline. We used these GENREs to identify subgroups of pathogens that share unique metabolic phenotypes and determined that pathogen physiological niche plays a role in the development of unique metabolic function. For example, we identified several unique metabolic phenotypes specific to stomach pathogens. We identified essential genes unique to stomach pathogens in silico and a corresponding inhibitory compound for a uniquely essential gene. We then validated our in silico predictions with an in vitro microbial growth assay. We demonstrated that the inhibition of a uniquely essential gene, thyX, inhibited growth of stomach-specific pathogens exclusively, indicating possible physiological location-specific targeting. This pioneering computational approach could lead to the identification of unique metabolic signatures to inform future targeted, physiological location-specific, antimicrobial therapies, reducing the need for broad-spectrum antibiotics.

Indexed as

Anti-Bacterial AgentsMetabolic Networks and PathwaysPhenotypeBacteriaDrug Resistance, BacterialGenome, BacterialHumansAnti-Bacterial Agents

Identifiers

PMID39556591
PMCPMC11611258

What OpenQuestion holds

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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.