Evidence map›Paper›PMID 26506097›Full record

ArticlePLoS pathogens2015

Systematic Identification of Cyclic-di-GMP Binding Proteins in Vibrio cholerae Reveals a Novel Class of Cyclic-di-GMP-Binding ATPases Associated with Type II Secretion Systems.

Kevin G Roelofs, Christopher J Jones, Sarah R Helman, Xiaoran Shang, Mona W Orr, Jonathan R Goodson, Michael Y Galperin, Fitnat H Yildiz, Vincent T Lee

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
7.7field-weighted citation impact, top 2% 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

76 citing papers in PubMed, 129 citations in OpenAlex.

  1. Article
  2. Article
  3. Discovery of Novel c-di-GMP-Related Genes inPathogens (Basel, Switzerland) · 2026
    Article
  4. Distinct PlzC mechanisms integrate chemotaxis and c-di-GMP signaling to regulateProceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  5. Nitric oxide promotes rapid development of motility to accelerate biofilm dispersal inProceedings of the National Academy of Sciences of the United States of America · 2025
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  7. Review
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  9. Review
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  11. Review
  12. FhlA is a Formate Binding Protein.bioRxiv : the preprint server for biology · 2024
    Article
  13. Article
  14. Article
  15. Review
  16. Autoinducer-2 promotes adherence ofApplied and environmental microbiology · 2023
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  17. Article
  18. Journal of bacteriology · 2023
    Article
  19. Article
  20. Article

16 more citing papers are in PubMed but not listed here.

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

9 authors at 3 institutions in 1 country.

Kevin G RoelofsDepartment of Cell Biology and Molecular Genetics, University of Maryland at College Park, Maryland, United States of America.
Christopher J JonesDepartment of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, California, United States of America.
Sarah R HelmanDepartment of Cell Biology and Molecular Genetics, University of Maryland at College Park, Maryland, United States of America.
Xiaoran ShangDepartment of Cell Biology and Molecular Genetics, University of Maryland at College Park, Maryland, United States of America.
Mona W OrrDepartment of Cell Biology and Molecular Genetics, University of Maryland at College Park, Maryland, United States of America.
Jonathan R GoodsonDepartment of Cell Biology and Molecular Genetics, University of Maryland at College Park, Maryland, United States of America.
Michael Y GalperinNational Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America.
Fitnat H YildizDepartment of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, California, United States of America.
Vincent T LeeDepartment of Cell Biology and Molecular Genetics, University of Maryland at College Park, Maryland, United States of America.
University of Maryland, College Park · USUniversity of California, Santa Cruz · USNational Institutes of Health · US

Funding

Vibrio cholerae c-diGMP signaling: Motile to biofilm transition and transmissionR01AI102584 · NIAID · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI YILDIZ, HAVVA FITNAT · 2013 to 2023
$6.5M
Training in Host-pathogens interactionsT32AI089621 · NIAID · UNIV OF MARYLAND, COLLEGE PARK · PI LEE, VINCENT T, MCIVER, KEVIN S. · 2010 to 2025
$2.1M
Vibrio cholerae c-diGMP signaling: motile to biofilm transition and transmissionR56AI102584 · NIAID · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI YILDIZ, HAVVA FITNAT · 2012 to 2012
$608k
High-throughput assay for protein-ligand interactionR21AI096083 · NIAID · UNIV OF MARYLAND, COLLEGE PARK · PI LEE, VINCENT T · 2011 to 2012
$398k
Intramural NIH HHSNIAID NIH HHS AI102584NIAID NIH HHS R01 AI102584NIAID NIH HHS R21 AI096083NIAID NIH HHS R21AI096083NIAID NIH HHS R56 AI102584NIAID NIH HHS T32 AI089621NIAID NIH HHS T32-AI089621
6 · The paper itself

Abstract

Cyclic-di-GMP (c-di-GMP) is a ubiquitous bacterial signaling molecule that regulates a variety of complex processes through a diverse set of c-di-GMP receptor proteins. We have utilized a systematic approach to identify c-di-GMP receptors from the pathogen Vibrio cholerae using the Differential Radial Capillary Action of Ligand Assay (DRaCALA). The DRaCALA screen identified a majority of known c-di-GMP binding proteins in V. cholerae and revealed a novel c-di-GMP binding protein, MshE (VC0405), an ATPase associated with the mannose sensitive hemagglutinin (MSHA) type IV pilus. The known c-di-GMP binding proteins identified by DRaCALA include diguanylate cyclases, phosphodiesterases, PilZ domain proteins and transcription factors VpsT and VpsR, indicating that the DRaCALA-based screen of open reading frame libraries is a feasible approach to uncover novel receptors of small molecule ligands. Since MshE lacks the canonical c-di-GMP-binding motifs, a truncation analysis was utilized to locate the c-di-GMP binding activity to the N-terminal T2SSE_N domain. Alignment of MshE homologs revealed candidate conserved residues responsible for c-di-GMP binding. Site-directed mutagenesis of these candidate residues revealed that the Arg9 residue is required for c-di-GMP binding. The ability of c-di-GMP binding to MshE to regulate MSHA dependent processes was evaluated. The R9A allele, in contrast to the wild type MshE, was unable to complement the ΔmshE mutant for the production of extracellular MshA to the cell surface, reduction in flagella swimming motility, attachment to surfaces and formation of biofilms. Testing homologs of MshE for binding to c-di-GMP identified the type II secretion ATPase of Pseudomonas aeruginosa (PA14_29490) as a c-di-GMP receptor, indicating that type II secretion and type IV pili are both regulated by c-di-GMP.

Indexed as

Adenosine TriphosphatasesCyclic GMPFimbriae, BacterialFimbriae ProteinsMannose-Binding LectinOpen Reading FramesType II Secretion SystemsVibrio choleraeAdenosine Triphosphatasesbis(3',5')-cyclic diguanylic acidCyclic GMPFimbriae ProteinsMannose-Binding LectinMshA protein, Vibrio choleraeType II Secretion Systems

Identifiers

PMID26506097
PMCPMC4624772
OpenAlexW1822002560

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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.