Evidence map›Paper›PMID 40139192›Full record

ArticleCell host & microbe2025

A thiouracil desulfurase protects Clostridioides difficile RNA from 4-thiouracil incorporation, providing a competitive advantage in the gut.

Matthew J Munneke, Yifeng Yuan, Eva C Preisner, Catherine D Shelton, Darian T Carroll, Nicole S Kirchoff, Ken P Dickson, Jose O Cantu, Martin V Douglass, M Wade Calcutt and 6 more

Abstract read
In one paragraph

Article in Cell host & microbe, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. DNA-utilization loci enable exogenous DNA metabolism in gut Bacteroidales.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. RNA modification is the mark and strategy for host-microbe interactions.Cellular and molecular life sciences : CMLS · 2025
    Review
  4. Article
  5. Review
  6. Scavenging a pyrimidine to thrive.Nature reviews. Microbiology · 2025
    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

16 authors.

Matthew J MunnekeDepartment of Pathology, Microbiology, and Immunology, Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232-7917, USA.
Yifeng YuanDepartment of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611, USA.
Eva C PreisnerCenter for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Catherine D SheltonDepartment of Pathology, Microbiology, and Immunology, Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232-7917, USA.
Darian T CarrollDepartment of Pathology, Microbiology, and Immunology, Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232-7917, USA.
Nicole S KirchoffDepartment of Pathology, Microbiology, and Immunology, Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232-7917, USA.
Ken P DicksonCenter for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Jose O CantuCenter for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Martin V DouglassDepartment of Pathology, Microbiology, and Immunology, Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232-7917, USA.
M Wade CalcuttMass Spectrometry Research Center, Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA.
Katherine N Gibson-CorleyDepartment of Pathology, Microbiology, and Immunology, Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232-7917, USA.
Maribeth R NicholsonDepartment of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232-7917, USA.
Mariana X ByndlossDepartment of Pathology, Microbiology, and Immunology, Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232-7917, USA; Howard Hughes Medical Institute, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Robert A BrittonCenter for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.
Valérie de Crécy-LagardDepartment of Microbiology and Cell Science, University of Florida, Gainesville, FL 32611, USA.
Eric P SkaarDepartment of Pathology, Microbiology, and Immunology, Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232-7917, USA. Electronic address: eric.skaar@vumc.org.

Funding

TRAINING PROGRAM IN ENVIRONMENTAL TOXICOLOGYT32ES007028 · NIEHS · VANDERBILT UNIVERSITY · PI F PETER Guengerich, Fiona Edith Harrison · 1985 to 2026
$15.7M
Organoid Cultivation CoreU19AI157981 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI MARESSO, ANTHONY W · 2021 to 2025
$12.4M
Vanderbilt Antibody and Antigen Discovery for Clostridioides difficile VaccinesU19AI174999 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Dana Borden Lacy · 2023 to 2026
$7.9M
Synthesis and function of Queuosine in BacteriaR01GM070641 · NIGMS · UNIVERSITY OF FLORIDA · PI DE CRECY-LAGARD, VALERIE A · 2006 to 2023
$5.3M
Mechanisms of Salmonella-mediated disruption of colonization resistance in the inflamed gutR01AI168302 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Mariana Xavier Byndloss · 2022 to 2026
$2.4M
Nutritional immunity and microbial competition during Clostridioides difficile infectionR01AI164587 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI SKAAR, ERIC P · 2022 to 2025
$2.4M
Texas Medical Center Training Program in Antimicrobial ResistanceT32AI141349 · NIAID · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI GARSIN, DANIELLE A · 2019 to 2023
$1.3M
Linking gene and function through comparative genomic and experimental approachesR35GM156215 · NIGMS · UNIVERSITY OF FLORIDA · PI Valerie A de Crecy-Lagard · 2025 to 2026
$1.3M
Immune, Microbial, and Metabolic Factors that Impact Clostridioides difficile and Inflammatory Bowel Disease in ChildrenK23AI156132 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI NICHOLSON, MARIBETH RUTH · 2021 to 2025
$876k
Clostridioides difficile nucleobase scavenging in the competitive gut environmentF31AI172352 · NIAID · VANDERBILT UNIVERSITY · PI MUNNEKE, MATTHEW · 2023 to 2024
$67k
NIAID NIH HHS F31 AI172352NIAID NIH HHS K23 AI156132NIAID NIH HHS R01 AI164587NIAID NIH HHS R01 AI168302NIAID NIH HHS T32 AI141349NIAID NIH HHS U19 AI157981NIAID NIH HHS U19 AI174999NIEHS NIH HHS T32 ES007028NIGMS NIH HHS R01 GM070641NIGMS NIH HHS R35 GM156215
6 · The paper itself

Abstract

Nucleotides are essential building blocks for major cellular macromolecules and are critical for life. Consequently, bacterial pathogens must acquire or synthesize nucleotides during infection. Clostridioides difficile is the most common hospital-acquired gastrointestinal infection, and nutrient acquisition is critical for pathogenesis. However, the impact of nucleotide metabolism on C. difficile infection remains unclear. Here, we discover that 4-thiouracil (4-TU), a pyrimidine analog present in the human gut, is toxic to commensal bacteria. 4-TU hijacks the uracil salvage pathway for incorporation into RNA through the uracil phosphoribosyltransferase activity encoded by PyrR and Upp. C. difficile can salvage 4-TU as a pyrimidine source through the enzymatic action of a thiouracil desulfurase (TudS), thereby contributing to C. difficile fitness in mice fed 4-TU or MiniBioreactor models of infection containing exogenous 4-TU. Collectively, these results reveal a molecular mechanism for C. difficile to utilize a poisonous pyrimidine analog in the vertebrate gut to outcompete commensal microbes.

Indexed as

Clostridioides difficileGastrointestinal TractRNA, BacterialThiouracilAnimalsBacterial ProteinsClostridium InfectionsHumansMicePentosyltransferases4-thiouracilBacterial ProteinsPentosyltransferasesRNA, BacterialThiouraciluracil phosphoribosyltransferase4-thiouracilClostridioides difficilenucleotidepyrimidine analogPyrRRNATudSUpp

Identifiers

PMID40139192
PMCPMC11985272

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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.