ArticleMolecular microbiology2017
c-di-AMP modulates Listeria monocytogenes central metabolism to regulate growth, antibiotic resistance and osmoregulation.
Article in Molecular microbiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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83 citing papers in PubMed, 138 citations in OpenAlex.
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- Structural and biochemical insights into the inhibition ofRSC chemical biology · 2026Article
- Altered abundance in cancer patients gut of diadenylate cyclase-encoding bacteria.Scientific reports · 2026Article
- Cyclic di-AMP inhibitsmBio · 2026Article
- Adaptive Tolerance of Listeria monocytogenes to Chemical Oxidants: Comparative Analysis of Transcriptomic Studies.Comprehensive reviews in food science and food safety · 2025Review
- TrkA ofMicrobiology (Reading, England) · 2025Article
- Cyclic-di-AMP modulates cellular turgor in response to defects in bacterial cell wall synthesis.Nature microbiology · 2025Article
- Phosphorylation State Dictates Bacterial Stressosome Assembly and Function.Research square · 2025Article
- Article
- Dysregulated biosynthesis and hydrolysis of cyclic-di-adenosine monophosphate impedes sporulation and butanol and acetone production inFrontiers in bioengineering and biotechnology · 2025Article
- Biofilm formation byProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Characterization of c-di-AMP signaling in the periodontal pathobiont, Treponema denticola.Molecular oral microbiology · 2024Article
- Molecular Targets inGenes · 2024Review
- The role ofJournal of bacteriology · 2024Article
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- Bacterial cell volume regulation and the importance of cyclic di-AMP.Microbiology and molecular biology reviews : MMBR · 2024Review
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- Allosteric regulation by c-di-AMP modulates a complete N-acetylglucosamine signaling cascade in Saccharopolyspora erythraea.Nature communications · 2024Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Cyclic diadenosine monophosphate (c-di-AMP) is a conserved nucleotide second messenger critical for bacterial growth and resistance to cell wall-active antibiotics. In Listeria monocytogenes, the sole diadenylate cyclase, DacA, is essential in rich, but not synthetic media and ΔdacA mutants are highly sensitive to the β-lactam antibiotic cefuroxime. In this study, loss of function mutations in the oligopeptide importer (oppABCDF) and glycine betaine importer (gbuABC) allowed ΔdacA mutants to grow in rich medium. Since oligopeptides were sufficient to inhibit growth of the ΔdacA mutant we hypothesized that oligopeptides act as osmolytes, similar to glycine betaine, to disrupt intracellular osmotic pressure. Supplementation with salt stabilized the ΔdacA mutant in rich medium and restored cefuroxime resistance. Additional suppressor mutations in the acetyl-CoA binding site of pyruvate carboxylase (PycA) rescued cefuroxime resistance and resulted in a 100-fold increase in virulence of the ΔdacA mutant. PycA is inhibited by c-di-AMP and these mutations prompted us to examine the role of TCA cycle enzymes. Inactivation of citrate synthase, but not down-stream enzymes suppressed ΔdacA phenotypes. These data suggested that c-di-AMP modulates central metabolism at the pyruvate node to moderate citrate production and indeed, the ΔdacA mutant accumulated six times the concentration of citrate present in wild-type bacteria.
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