ArticleInfection and immunity2014
DhhP, a cyclic di-AMP phosphodiesterase of Borrelia burgdorferi, is essential for cell growth and virulence.
Article in Infection and immunity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 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
60 citing papers in PubMed, 89 citations in OpenAlex.
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- Altered abundance in cancer patients gut of diadenylate cyclase-encoding bacteria.Scientific reports · 2026Article
- Regulation of potassium homeostasis inFrontiers in microbiology · 2026Article
- Borrelia burgdorferi c-di-AMP is a key extracellular pathogen-associated molecular pattern to elicit type I interferon responses in mammalian hosts.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Cyclic-di-AMP modulates cellular turgor in response to defects in bacterial cell wall synthesis.Nature microbiology · 2025Article
- Review
- 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
- Structural and functional investigation of the DHH/DHHA1 family proteins in Deinococcus radiodurans.Nucleic acids research · 2024Article
- Bacterial cell volume regulation and the importance of cyclic di-AMP.Microbiology and molecular biology reviews : MMBR · 2024Review
- Synthesis and degradation of the cyclic dinucleotide messenger c-di-AMP in the hyperthermophilic archaeon Pyrococcus yayanosii.Protein science : a publication of the Protein Society · 2023Article
- All DACs in a Row: Domain Architectures of Bacterial and Archaeal Diadenylate Cyclases.Journal of bacteriology · 2023Review
- Genomic Distribution of Pro-VirulentInternational journal of molecular sciences · 2023Article
- C-di-AMP Is a Second Messenger inMicroorganisms · 2023Article
- An atypical GdpP enzyme linking cyclic nucleotide metabolism to osmotic tolerance and gene regulation inFrontiers in microbiology · 2023Article
- Regulatory mechanisms of exopolysaccharide synthesis and biofilm formation in Streptococcus mutans.Journal of oral microbiology · 2023Review
- c-di-AMP signaling is required for bile salt resistance, osmotolerance, and long-term host colonization byScience signaling · 2022Article
- The role of bacterial cyclic di-adenosine monophosphate in the host immune response.Frontiers in microbiology · 2022Review
- c-di-AMP Is Essential for the Virulence ofInfection and immunity · 2021Article
- The c-di-AMP signaling system influences stress tolerance and biofilm formation of Streptococcus mitis.MicrobiologyOpen · 2021Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Cyclic di-AMP (c-di-AMP) is a recently discovered second messenger in bacteria. Most of work on c-di-AMP signaling has been done in Gram-positive bacteria, firmicutes, and actinobacteria, where c-di-AMP signaling pathways affect potassium transport, cell wall structure, and antibiotic resistance. Little is known about c-di-AMP signaling in other bacteria. Borrelia burgdorferi, the causative agent of Lyme disease, is a spirochete that has a Gram-negative dual membrane. In this study, we demonstrated that B. burgdorferi BB0619, a DHH-DHHA1 domain protein (herein designated DhhP), functions as c-di-AMP phosphodiesterase. Recombinant DhhP hydrolyzed c-di-AMP to pApA in a Mn(2+)- or Mg(2+)-dependent manner. In contrast to c-di-AMP phosphodiesterases reported thus far, DhhP appears to be essential for B. burgdorferi growth both in vitro and in the mammalian host. Inactivation of the chromosomal dhhP gene could be achieved only in the presence of a plasmid-encoded inducible dhhP gene. The conditional dhhP mutant had a dramatic increase in intracellular c-di-AMP level in comparison to the isogenic wild-type strain. Unlike what has been observed in Gram-positive bacteria, elevated cellular c-di-AMP in B. burgdorferi did not result in an increased resistance to β-lactamase antibiotics, suggesting that c-di-AMP's functions in spirochetes differ from those in Gram-positive bacteria. In addition, the dhhP mutant was defective in induction of the σ(S) factor, RpoS, and the RpoS-dependent outer membrane virulence factor OspC, which uncovers an important role of c-di-AMP in B. burgdorferi virulence.
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Registered trials
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.