ArticleProceedings of the National Academy of Sciences of the United States of America2015
An HD-domain phosphodiesterase mediates cooperative hydrolysis of c-di-AMP to affect bacterial growth and virulence.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
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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.
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Who cites it
128 citing papers in PubMed, 200 citations in OpenAlex.
- Cyclic di-AMP signaling and regulation inmSphere · 2026Review
- Roles of divalent metals in the regulation of cyclic di-GMP signaling in bacteria.Journal of bacteriology · 2026Review
- High-quality draft genome of the Listeria monocytogenes, one more vaccine strain against livestock listeriosis.Scientific data · 2026Article
- Structural and biochemical insights into the inhibition ofRSC chemical biology · 2026Article
- Characterization of a novel cell wall-associated nucleotidase of Enterococcus faecalis that degrades extracellular c-di-AMP.PLoS pathogens · 2026Article
- Orn-mediated c-di-GMP regulates the CRISPR-Cas system to confer stress response in Mycobacterium tuberculosis.Nucleic acids research · 2026Article
- Cyclic di-AMP inhibitsmBio · 2026Article
- The c-di-AMP binding protein NadD from Mesomycoplasma ovipneumoniae functions as a phosphodiesterase that inhibits host inflammatory responses.Veterinary research · 2026Article
- Exploring the evolutionary divergence of cyclic di-nucleotide signaling in diverse mycobacterial species.Archives of microbiology · 2026Article
- Impact of c-di-AMP Accumulation, L-cysteine, and Oxygen on Catalase Activity and Oxidative Stress Resistance ofMicroorganisms · 2025Article
- Formation of Mono-Organismal and MixedMicroorganisms · 2025Article
- Review
- Dysregulated biosynthesis and hydrolysis of cyclic-di-adenosine monophosphate impedes sporulation and butanol and acetone production inFrontiers in bioengineering and biotechnology · 2025Article
- C-di-AMP accumulation disrupts glutathione metabolism inInfection and immunity · 2024Article
- Characterization of c-di-AMP signaling in the periodontal pathobiont, Treponema denticola.Molecular oral microbiology · 2024Article
- The role ofJournal of bacteriology · 2024Article
- Structural and functional investigation of the DHH/DHHA1 family proteins in Deinococcus radiodurans.Nucleic acids research · 2024Article
- Review
- Bacterial cell volume regulation and the importance of cyclic di-AMP.Microbiology and molecular biology reviews : MMBR · 2024Review
- Bioinformatic prediction of proteins relevant to functions of the bacterial OLE ribonucleoprotein complex.mSphere · 2024Article
68 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The nucleotide cyclic di-3',5'- adenosine monophosphate (c-di-AMP) was recently identified as an essential and widespread second messenger in bacterial signaling. Among c-di-AMP-producing bacteria, altered nucleotide levels result in several physiological defects and attenuated virulence. Thus, a detailed molecular understanding of c-di-AMP metabolism is of both fundamental and practical interest. Currently, c-di-AMP degradation is recognized solely among DHH-DHHA1 domain-containing phosphodiesterases. Using chemical proteomics, we identified the Listeria monocytogenes protein PgpH as a molecular target of c-di-AMP. Biochemical and structural studies revealed that the PgpH His-Asp (HD) domain bound c-di-AMP with high affinity and specifically hydrolyzed this nucleotide to 5'-pApA. PgpH hydrolysis activity was inhibited by ppGpp, indicating a cross-talk between c-di-AMP signaling and the stringent response. Genetic analyses supported coordinated regulation of c-di-AMP levels in and out of the host. Intriguingly, a L. monocytogenes mutant that lacks c-di-AMP phosphodiesterases exhibited elevated c-di-AMP levels, hyperinduced a host type-I IFN response, and was significantly attenuated for infection. Furthermore, PgpH homologs, which belong to the 7TMR-HD family, are widespread among hundreds of c-di-AMP synthesizing microorganisms. Thus, PgpH represents a broadly conserved class of c-di-AMP phosphodiesterase with possibly other physiological functions in this crucial signaling network.
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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.