ArticleMolecular microbiology2014
Deletion of the cyclic di-AMP phosphodiesterase gene (cnpB) in Mycobacterium tuberculosis leads to reduced virulence in a mouse model of infection.
Article in Molecular microbiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed.
- Altered abundance in cancer patients gut of diadenylate cyclase-encoding bacteria.Scientific reports · 2026Article
- Exploring the evolutionary divergence of cyclic di-nucleotide signaling in diverse mycobacterial species.Archives of microbiology · 2026Article
- Functional analyses of bacterial NanoRNase B proteins reveals defining features of this enzyme family.Nucleic acids research · 2025Article
- Cyclic Di-AMP Affects Cell Membrane Integrity of Streptococcus pneumoniae.Molecular microbiology · 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
- Cyclic di-AMP regulates genome stability and drug resistance inPNAS nexus · 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
- Elucidating the role of c-di-AMP inHeliyon · 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
- Fighting Tuberculosis: In Search of a BCG Replacement.Microorganisms · 2022Review
- Nano-RNases: oligo- or dinucleases?FEMS microbiology reviews · 2022Review
- [Advances in Research on the Role of Bacterial c-di-AMP in Host Immunity].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2022Review
- c-di-AMP signaling is required for bile salt resistance, osmotolerance, and long-term host colonization byScience signaling · 2022Article
- c-di-AMP signaling plays important role in determining antibiotic tolerance phenotypes of Mycobacterium smegmatis.Scientific reports · 2022Article
18 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors.
Funding
Abstract
Tuberculosis (TB) remains a major cause of morbidity and mortality worldwide. The pathogenesis by the causative agent, Mycobacterium tuberculosis, is still not fully understood. We have previously reported that M. tuberculosis Rv3586 (disA) encodes a diadenylate cyclase, which converts ATP to cyclic di-AMP (c-di-AMP). In this study, we demonstrated that a protein encoded by Rv2837c (cnpB) possesses c-di-AMP phosphodiesterase activity and cleaves c-di-AMP exclusively to AMP. Our results showed that in M. tuberculosis, deletion of disA abolished bacterial c-di-AMP production, whereas deletion of cnpB significantly enhanced the bacterial c-di-AMP accumulation and secretion. The c-di-AMP levels in both mutants could be corrected by expressing the respective gene. We also found that macrophages infected with ΔcnpB secreted much higher levels of IFN-β than those infected with the wild type (WT) or the complemented mutant. Interestingly, mice infected with M. tuberculosis ΔcnpB displayed significantly reduced inflammation, less bacterial burden in the lungs and spleens, and extended survival compared with those infected with the WT or the complemented mutant. These results indicate that deletion of cnpB results in attenuated virulence, which is correlated with elevated c-di-AMP levels.
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