Evidence map›Paper›PMID 30699117›Full record

ArticlePloS one2019

Impact of CodY protein on metabolism, sporulation and virulence in Clostridioides difficile ribotype 027.

Nadine Daou, Yuanguo Wang, Vladimir M Levdikov, Madhumitha Nandakumar, Jonathan Livny, Laurent Bouillaut, Elena Blagova, Keshan Zhang, Boris R Belitsky, Kyu Rhee and 3 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

28 citing papers in PubMed, 34 citations in OpenAlex.

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  13. The pH-responsive SmrR-SmrT system modulatesInfection and immunity · 2024
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  14. Regulatory transcription factors ofCritical reviews in microbiology · 2023
    Review
  15. Microbiology (Reading, England) · 2023
    Review
  16. Review
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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

13 authors at 5 institutions in 2 countries.

Nadine DaouDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, United States of America.
Yuanguo WangDepartment of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, United States of America.
Vladimir M LevdikovStructural Biology Laboratory, Department of Chemistry, University of York, York, United Kingdom.
Madhumitha NandakumarDepartment of Medicine, Division of Infectious Diseases, Weill Cornell Medical College, New York, NY, United States of America.
Jonathan LivnyBroad Institute of MIT and Harvard, Cambridge, MA, United States of America.
Laurent BouillautDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, United States of America.
Elena BlagovaStructural Biology Laboratory, Department of Chemistry, University of York, York, United Kingdom.
Keshan ZhangDepartment of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, United States of America.
Boris R BelitskyDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, United States of America.
Kyu RheeDepartment of Medicine, Division of Infectious Diseases, Weill Cornell Medical College, New York, NY, United States of America.
Anthony J WilkinsonStructural Biology Laboratory, Department of Chemistry, University of York, York, United Kingdom.
Xingmin SunDepartment of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, United States of America.
Abraham L SonensheinDepartment of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, United States of America.ORCID 0000-0002-9113-0358
Tufts University · USUniversity of York · GBCornell University · USBroad Institute · USUniversity of South Florida · US

Funding

ISOLATION OF EARLY SPORULATION GENESR01GM042219 · NIGMS · TUFTS UNIVERSITY BOSTON · PI SONENSHEIN, ABRAHAM LINCOLN · 1989 to 2015
$5.8M
Signaling pathway of TNF-alpha production and Clostridium difficile infection (CDK01DK092352 · NIDDK · UNIVERSITY OF SOUTH FLORIDA · PI SUN, XINGMIN · 2012 to 2016
$470k
Biotechnology and Biological Sciences Research Council BBS/B/1213XNIDDK NIH HHS K01 DK092352NIGMS NIH HHS R01 GM042219
6 · The paper itself

Abstract

Toxin synthesis and endospore formation are two of the most critical factors that determine the outcome of infection by Clostridioides difficile. The two major toxins, TcdA and TcdB, are the principal factors causing damage to the host. Spores are the infectious form of C. difficile, permit survival of the bacterium during antibiotic treatment and are the predominant cell form that leads to recurrent infection. Toxin production and sporulation have their own specific mechanisms of regulation, but they share negative regulation by the global regulatory protein CodY. Determining the extent of such regulation and its detailed mechanism is important for understanding the linkage between two apparently independent biological phenomena and raises the possibility of creating new ways of limiting infection. The work described here shows that a codY null mutant of a hypervirulent (ribotype 027) strain is even more virulent than its parent in a mouse model of infection and that the mutant expresses most sporulation genes prematurely during exponential growth phase. Moreover, examining the expression patterns of mutants producing CodY proteins with different levels of residual activity revealed that expression of the toxin genes is dependent on total CodY inactivation, whereas most sporulation genes are turned on when CodY activity is only partially diminished. These results suggest that, in wild-type cells undergoing nutrient limitation, sporulation genes can be turned on before the toxin genes.

Indexed as

RibotypingAmino Acid SequenceAnimalsBacterial ProteinsBacterial ToxinsBiosynthetic PathwaysClostridioides difficileDiarrheaEthanolamineGene Expression Regulation, BacterialGenes, BacterialMice, Inbred C57BLMultigene FamilyOperonPoint MutationProtein DomainsBacterial ProteinsBacterial ToxinsEthanolamine

Identifiers

PMID30699117
PMCPMC6353076
OpenAlexW2913919892

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.