Evidence map›Paper›PMID 23716572›Full record

ArticlemBio2013

Cyclic di-AMP is critical for Listeria monocytogenes growth, cell wall homeostasis, and establishment of infection.

Chelsea E Witte, Aaron T Whiteley, Thomas P Burke, John-Demian Sauer, Daniel A Portnoy, Joshua J Woodward

Open access · goldAbstract read
In one paragraph

Article in mBio, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers.

0numbers the graph read from it
0cells of the map it votes in
123citing papers in PubMed
10.3field-weighted citation impact, top 1% 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

123 citing papers in PubMed, 202 citations in OpenAlex.

  1. Mislocalization of PBPs inMicrobiology spectrum · 2026
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  7. Regulation of potassium homeostasis inFrontiers in microbiology · 2026
    Article
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  9. Article
  10. Article
  11. Cyclic di-AMP alleviates periodontitis by activating PI3K/Akt/Nrf2 pathways.Frontiers in cellular and infection microbiology · 2025
    Article
  12. Article
  13. Article
  14. The role ofJournal of bacteriology · 2024
    Article
  15. Bacterial cell volume regulation and the importance of cyclic di-AMP.Microbiology and molecular biology reviews : MMBR · 2024
    Review
  16. Nucleotides as Bacterial Second Messengers.Molecules (Basel, Switzerland) · 2023
    Review
  17. Loss of Pde1 function acts as an evolutionary gateway to penicillin resistance inProceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  18. Review
  19. Article
  20. Article

63 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

6 authors at 1 institution in 1 country.

Chelsea E WitteGraduate Group in Microbiology, University of California, Berkeley, Berkeley, California, USA.
Aaron T Whiteley
Thomas P Burke
John-Demian Sauer
Daniel A Portnoy
Joshua J Woodward
University of California, Berkeley · US

Funding

The role of Listeria cyclic-di-AMP during infection and immunityP01AI063302 · NIAID · UNIVERSITY OF CALIFORNIA BERKELEY · PI STANLEY, SARAH A · 2004 to 2025
$45.5M
THE MOLECULAR BASIS OF CELL FUNCTIONT32GM007232 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI BILDER, DAVID, UNAL, ELCIN · 1985 to 2022
$36.4M
Listeria Hemolysis and Escape From a VacuoleR01AI027655 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI DANIEL A PORTNOY · 1993 to 2026
$10.1M
NIAID NIH HHS 1P01 AI63302NIAID NIH HHS 1R01 AI27655NIAID NIH HHS P01 AI063302NIAID NIH HHS R01 AI027655PHS HHS F32 A184372
6 · The paper itself

Abstract

Listeria monocytogenes infection leads to robust induction of an innate immune signaling pathway referred to as the cytosolic surveillance pathway (CSP), characterized by expression of beta interferon (IFN-β) and coregulated genes. We previously identified the IFN-β stimulatory ligand as secreted cyclic di-AMP. Synthesis of c-di-AMP in L. monocytogenes is catalyzed by the diadenylate cyclase DacA, and multidrug resistance transporters are necessary for secretion. To identify additional bacterial factors involved in L. monocytogenes detection by the CSP, we performed a forward genetic screen for mutants that induced altered levels of IFN-β. One mutant that stimulated elevated levels of IFN-β harbored a transposon insertion in the gene lmo0052. Lmo0052, renamed here PdeA, has homology to a cyclic di-AMP phosphodiesterase, GdpP (formerly YybT), of Bacillus subtilis and is able to degrade c-di-AMP to the linear dinucleotide pApA. Reduction of c-di-AMP levels by conditional depletion of the di-adenylate cyclase DacA or overexpression of PdeA led to marked decreases in growth rates, both in vitro and in macrophages. Additionally, mutants with altered levels of c-di-AMP had different susceptibilities to peptidoglycan-targeting antibiotics, suggesting that the molecule may be involved in regulating cell wall homeostasis. During intracellular infection, increases in c-di-AMP production led to hyperactivation of the CSP. Conditional depletion of dacA also led to increased IFN-β expression and a concomitant increase in host cell pyroptosis, a result of increased bacteriolysis and subsequent bacterial DNA release. These data suggest that c-di-AMP coordinates bacterial growth, cell wall stability, and responses to stress and plays a crucial role in the establishment of bacterial infection.

Indexed as

AnimalsBacterial ProteinsCell WallDinucleoside PhosphatesDNA Transposable ElementsFemaleGene Expression Regulation, BacterialGene Knockout TechniquesHomeostasisListeria monocytogenesListeriosisMiceMice, Inbred C57BLMutagenesis, InsertionalVirulence FactorsBacterial Proteinscyclic diadenosine phosphateDinucleoside PhosphatesDNA Transposable ElementsVirulence Factors

Identifiers

PMID23716572
PMCPMC3663569
OpenAlexW2136361611

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.