Evidence map›Paper›PMID 40397889›Full record

ArticlePLoS pathogens2025

Unique growth and morphology properties of Clade 5 Clostridioides difficile strains revealed by single-cell time-lapse microscopy.

John W Ribis, César Nieto, Nicholas V DiBenedetto, Anchal Mehra, Pola Kuhn, Qiwen Dong, Irene Nagawa, Imane El Meouche, Bree B Aldridge, Mary J Dunlop and 3 more

Abstract read
In one paragraph

Article in PLoS pathogens, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Article
  2. Phase variable colony morphotypes ofInfection and immunity · 2026
    Article
  3. Article
  4. Article
  5. Contact dependent suppression ofbioRxiv : the preprint server for biology · 2026
    Article
  6. CenIR, an essential BlaIR-family regulatory system inbioRxiv : the preprint server for biology · 2026
    Article
  7. Journal of bacteriology · 2026
    Article
  8. Phase variable colony morphotypes ofbioRxiv : the preprint server for biology · 2026
    Article
  9. Article
  10. bioRxiv : the preprint server for biology · 2025
    Article
  11. Phenotypic analysis of variousApplied and environmental microbiology · 2025
    Article
  12. Article
  13. Unique growth and morphology properties of Clade 5bioRxiv : the preprint server for biology · 2025
    Article
  14. Article
  15. Phenotypic analysis of variousbioRxiv : the preprint server for biology · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

John W RibisDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
César NietoDepartment of Electrical and Computer Engineering, University of Delaware, Newark, Delaware, United States of America.
Nicholas V DiBenedettoDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
Anchal MehraDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States of America.
Pola KuhnDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
Qiwen DongDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
Irene NagawaDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
Imane El MeoucheDepartment of Biomedical Engineering, Tufts University School of Engineering, Medford, Massachusetts, United States of America.
Bree B AldridgeDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.
Mary J DunlopBiomedical Engineering, Boston University, Boston, Massachusetts United States of America.
Rita TamayoDepartment of Microbiology and Immunology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States of America.
Abhyudai SinghDepartment of Electrical and Computer Engineering, University of Delaware, Newark, Delaware, United States of America.
Aimee ShenDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, United States of America.ORCID 0000-0002-9786-5742

Funding

MOLECULAR ANALYSIS OF MICROBIAL PATHOGENST32AI007422 · NIAID · TUFTS UNIVERSITY BOSTON · PI Ralph R. Isberg · 1992 to 2026
$5.7M
Spore Assembly in Clostridium DifficileR01AI122232 · NIAID · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI SHEN, AIMEE · 2016 to 2025
$4.2M
MOLECULAR GENETICS OF BASIC CELL FUNCTIONST32GM007310 · NIGMS · TUFTS UNIVERSITY BOSTON · PI CAMILLI, ANDREW · 1987 to 2020
$3.9M
Global regulation in Clostridium difficile via phase variation of cyclic diguanylate signalingR01AI143638 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI TAMAYO, RITA · 2019 to 2023
$2.5M
Generalized fluctuation test for deciphering phenotypic switching within cell populationsR35GM148351 · NIGMS · UNIVERSITY OF DELAWARE · PI Abhyudai Singh · 2023 to 2026
$1.6M
Cell Division in ClostridioidesdifficileR37AI122232 · NIAID · TUFTS UNIVERSITY BOSTON · PI Aimee Shen · 2026 to 2026
$509k
Linking Gene Expression Profiles to Cell Fate in Clostridioides difficile Using Time-Lapse MicroscopyR21AI153853 · NIAID · TUFTS UNIVERSITY BOSTON · PI SHEN, AIMEE · 2021 to 2022
$462k
NIAID NIH HHS R01 AI122232NIAID NIH HHS R01 AI143638NIAID NIH HHS R21 AI153853NIAID NIH HHS R37 AI122232NIAID NIH HHS T32 AI007422NIGMS NIH HHS R35 GM148351NIGMS NIH HHS T32 GM007310
6 · The paper itself

Abstract

Clostridioides difficile is a gastrointestinal pathogen of both humans and agricultural animals and thus a major One Health threat. The C. difficile species consists of five main clades, with Clade 5 currently undergoing speciation from Clades 1-4. Since Clade 5 strains are highly prevalent in agricultural animals and a frequent cause of zoonotic infections, these strains may have evolved phenotypes that distinguish them from Clade 1-4 strains. Here, we compare the growth properties of Clade 5 strains to those of Clade 1-4 strains using anaerobic time-lapse microscopy coupled with automated image analysis. Our analyses indicate that Clade 5 strains grow faster and are more likely to form long chains of cells than Clade 1-4 strains. Using comparative genomic and CRISPRi analyses, we show that the chaining phenotype of Clade 5 strains is driven by the orientation of the invertible cmr switch sequence, with chaining strains exhibiting a bias to the cmr-ON state. Interestingly, Clade 5 strains with a bias towards the cmr-ON state shifted to a largely cmr-OFF state during murine infection, suggesting that the cmr-OFF state is under positive selection during infection. Collectively, our data reveal that Clade 5 strains have distinct growth properties, which may allow them to inhabit diverse ecological niches.

Indexed as

Clostridioides difficileClostridium InfectionsAnimalsHumansMicePhenotypeSingle-Cell AnalysisTime-Lapse Imaging

Identifiers

PMID40397889
PMCPMC12140426

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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.