Evidence map›Paper›PMID 35953658›Full record

ArticleNature microbiology2022

Diadenosine tetraphosphate regulates biosynthesis of GTP in Bacillus subtilis.

Pietro I Giammarinaro, Megan K M Young, Wieland Steinchen, Christopher-Nils Mais, Georg Hochberg, Jin Yang, David M Stevenson, Daniel Amador-Noguez, Anja Paulus, Jue D Wang and 1 more

Open access · greenAbstract read
In one paragraph

Article in Nature microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.9field-weighted citation impact, top 8% 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

29 citing papers in PubMed, 37 citations in OpenAlex.

  1. Loss of the ApJournal of bacteriology · 2026
    Article
  2. Article
  3. Molecular insights into the promiscuous ApThe Journal of biological chemistry · 2026
    Article
  4. Article
  5. ApaH decaps NpNature chemical biology · 2026
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  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Prokaryotic homeostasis - a solution to thrive and survive.Frontiers in molecular biosciences · 2025
    Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. A journey into the regulatory secrets of theFrontiers in pharmacology · 2024
    Review
  19. Review
  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

11 authors at 2 institutions in 2 countries.

Pietro I Giammarinaro *Department of Chemistry and Center for Synthetic Microbiology, Philipps University Marburg, Marburg, Germany.
Megan K M Young *Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.
Wieland SteinchenDepartment of Chemistry and Center for Synthetic Microbiology, Philipps University Marburg, Marburg, Germany.
Christopher-Nils MaisDepartment of Chemistry and Center for Synthetic Microbiology, Philipps University Marburg, Marburg, Germany.ORCID http://orcid.org/0000-0003-1927-2885
Georg HochbergDepartment of Chemistry and Center for Synthetic Microbiology, Philipps University Marburg, Marburg, Germany.
Jin YangDepartment of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0003-3442-5608
David M StevensonDepartment of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.
Daniel Amador-NoguezDepartment of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.ORCID http://orcid.org/0000-0002-3568-3070
Anja PaulusDepartment of Chemistry and Center for Synthetic Microbiology, Philipps University Marburg, Marburg, Germany.
Jue D WangDepartment of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA. wang@bact.wisc.edu.ORCID http://orcid.org/0000-0003-1503-170X
Gert BangeDepartment of Chemistry and Center for Synthetic Microbiology, Philipps University Marburg, Marburg, Germany. gert.bange@synmikro.uni-marburg.de.ORCID http://orcid.org/0000-0002-7826-0932
Loewe Center for Synthetic Microbiology · DEUniversity of Wisconsin–Madison · US

Funding

The critical roles of (p)ppGpp in homeostasis and antibiotic tolerance in Gram positive bacteriaR35GM127088 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI Jue D. Wang · 2018 to 2026
$3.9M
Howard Hughes Medical InstituteNIGMS NIH HHS R35 GM127088
6 · The paper itself

Abstract

Diadenosine tetraphosphate (Ap4A) is a putative second messenger molecule that is conserved from bacteria to humans. Nevertheless, its physiological role and the underlying molecular mechanisms are poorly characterized. We investigated the molecular mechanism by which Ap4A regulates inosine-5'-monophosphate dehydrogenase (IMPDH, a key branching point enzyme for the biosynthesis of adenosine or guanosine nucleotides) in Bacillus subtilis. We solved the crystal structure of BsIMPDH bound to Ap4A at a resolution of 2.45 Å to show that Ap4A binds to the interface between two IMPDH subunits, acting as the glue that switches active IMPDH tetramers into less active octamers. Guided by these insights, we engineered mutant strains of B. subtilis that bypass Ap4A-dependent IMPDH regulation without perturbing intracellular Ap4A pools themselves. We used metabolomics, which suggests that these mutants have a dysregulated purine, and in particular GTP, metabolome and phenotypic analysis, which shows increased sensitivity of B. subtilis IMPDH mutant strains to heat compared with wild-type strains. Our study identifies a central role for IMPDH in remodelling metabolism and heat resistance, and provides evidence that Ap4A can function as an alarmone.

Indexed as

Bacillus subtilisDinucleoside PhosphatesGuanosine Triphosphatediadenosine tetraphosphateDinucleoside PhosphatesGuanosine Triphosphate

Identifiers

PMID35953658
PMCPMC10439310
OpenAlexW4292865330

What OpenQuestion holds

Textmetadata
LicenceTDM
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.