Evidence map›Paper›PMID 25817996›Full record

ArticleThe Journal of biological chemistry2015

Dimeric c-di-GMP is required for post-translational regulation of alginate production in Pseudomonas aeruginosa.

John C Whitney, Gregory B Whitfield, Lindsey S Marmont, Patrick Yip, A Mirela Neculai, Yuri D Lobsanov, Howard Robinson, Dennis E Ohman, P Lynne Howell

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

56 citing papers in PubMed, 103 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Microbiology (Reading, England) · 2026
    Article
  5. Article
  6. UnderstandingMicroorganisms · 2026
    Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Advances in alginate biosynthesis: regulation and production inFrontiers in bioengineering and biotechnology · 2025
    Review
  13. Busulfan inhibitsFrontiers in cellular and infection microbiology · 2025
    Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. 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

9 authors at 4 institutions in 2 countries.

John C WhitneyFrom the Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada, the Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Gregory B WhitfieldFrom the Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada, the Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Lindsey S MarmontFrom the Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada, the Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Patrick YipFrom the Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
A Mirela NeculaiFrom the Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
Yuri D LobsanovFrom the Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada.
Howard Robinsonthe Photon Sciences Division, Brookhaven National Laboratory, Upton, New York 11973-5000, and.
Dennis E Ohmanthe Department of Microbiology and Immunology, Virginia Commonwealth University Medical Center and McGuire Veterans Affairs Medical Center, Richmond, Virginia 23298-0678.
P Lynne HowellFrom the Program in Molecular Structure and Function, Hospital for Sick Children, Toronto, Ontario M5G 0A4, Canada, the Department of Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada, howell@sickkids.ca.
Hospital for Sick Children · CAUniversity of Toronto · CABrookhaven National Laboratory · USVirginia Commonwealth University Medical Center · US

Funding

GENETICS OF ALGINATE BIOSYNTHESIS IN P. AERUGINOSAR01AI019146 · NIAID · VIRGINIA COMMONWEALTH UNIVERSITY · PI OHMAN, DENNIS EDWARD · 1985 to 2011
$2.7M
Activation of Alginate Genes in Pseudomonas aeruginosaR56AI019146 · NIAID · VIRGINIA COMMONWEALTH UNIVERSITY · PI OHMAN, DENNIS EDWARD · 2006 to 2013
$682k
Pathogenic Mechanism for Lung Infection in Mucoid PseudomonasI01BX000477 · VA · VA VETERANS ADMINISTRATION HOSPITAL · PI OHMAN, DENNIS EDWARD, ZHOU, HUIPING · 2011 to 2025
–
BLRD VA I01 BX000477Canadian Institutes of Health Research MT13337NIAID NIH HHS AI-19146NIAID NIH HHS R01 AI019146NIAID NIH HHS R56 AI019146
6 · The paper itself

Abstract

Pseudomonas aeruginosa is an opportunistic human pathogen that secretes the exopolysaccharide alginate during infection of the respiratory tract of individuals afflicted with cystic fibrosis and chronic obstructive pulmonary disease. Among the proteins required for alginate production, Alg44 has been identified as an inner membrane protein whose bis-(3',5')-cyclic dimeric guanosine monophosphate (c-di-GMP) binding activity post-translationally regulates alginate secretion. In this study, we report the 1.8 Å crystal structure of the cytoplasmic region of Alg44 in complex with dimeric self-intercalated c-di-GMP and characterize its dinucleotide-binding site using mutational analysis. The structure shows that the c-di-GMP binding region of Alg44 adopts a PilZ domain fold with a dimerization mode not previously observed for this family of proteins. Calorimetric binding analysis of residues in the c-di-GMP binding site demonstrate that mutation of Arg-17 and Arg-95 alters the binding stoichiometry between c-di-GMP and Alg44 from 2:1 to 1:1. Introduction of these mutant alleles on the P. aeruginosa chromosome show that the residues required for binding of dimeric c-di-GMP in vitro are also required for efficient alginate production in vivo. These results suggest that the dimeric form of c-di-GMP represents the biologically active signaling molecule needed for the secretion of an important virulence factor produced by P. aeruginosa.

Indexed as

Protein MultimerizationAlginatesBacterial ProteinsBinding SitesCrystallography, X-RayCyclic GMPGlucuronic AcidHexuronic AcidsHumansMembrane ProteinsMutationProtein Structure, QuaternaryPseudomonas aeruginosaVirulence FactorsAlg44 protein, Pseudomonas aeruginosaAlginatesBacterial Proteinsbis(3',5')-cyclic diguanylic acidCyclic GMPGlucuronic AcidHexuronic AcidsMembrane ProteinsVirulence Factorsalginatebiofilmcrystal structurecyclic di-GMP (c-di-GMP)exopolysaccharideisothermal titration calorimetry (ITC)PilZPseudomonas aeruginosa (P. aeruginosa)

Identifiers

PMID25817996
PMCPMC4432266
OpenAlexW2144367857

What OpenQuestion holds

Textmetadata
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.