Bacterial cell volume regulation and the importance of cyclic di-AMP
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SUMMARY: Nucleotide-derived second messengers are present in all domains of life. In prokaryotes, most of their functionality is associated with general lifestyle and metabolic adaptations, often in response to environmental fluctuations of physical parameters. In the last two decades, cyclic di-AMP has emerged as an important signaling nucleotide in many prokaryotic lineages, including Firmicutes, Actinobacteria, and Cyanobacteria. Its importance is highlighted by the fact that both the lack and overproduction of cyclic di-AMP affect viability of prokaryotes that utilize cyclic di-AMP, and that it generates a strong innate immune response in eukaryotes. In bacteria that produce the second messenger, most molecular targets of cyclic di-AMP are associated with cell volume control. Besides, other evidence links the second messenger to cell wall remodeling, DNA damage repair, sporulation, central metabolism, and the regulation of glycogen turnover. In this review, we take a biochemical, quantitative approach to address the main cellular processes that are directly regulated by cyclic di-AMP and show that these processes are very connected and require regulation of a similar set of proteins to which cyclic di-AMP binds. Altogether, we argue that cyclic di-AMP is a master regulator of cell volume and that other cellular processes can be connected with cyclic di-AMP through this core function. We further highlight important directions in which the cyclic di-AMP field has to develop to gain a full understanding of the cyclic di-AMP signaling network and why some processes are regulated, while others are not.
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K+ maintains osmotic balance and is an important contributor to the membrane potential.
“This dominant cation maintains osmotic balance7,46,47 and is an important contributor to the membrane potential.48”
From Metals in Motion: Understanding Labile Metal Pools in Bacteria (2025) · cites this paper as [46]
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BackgroundAssessment of the Requirements for Magnesium Transporters in Bacillus subtilis
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Metals in Motion: Understanding Labile Metal Pools in Bacteria
Helmann, J. D. (2025) · Biochemistry · doi:10.1021/acs.biochem.4c00726 · Cited by 49 · see citing works
- Authors
- Foster, A. J., van den Noort, M., & Poolman, B.
- Affiliations
- University of Groningen (NL)
- Department of Biochemistry, Groningen Biomolecular Science and Biotechnology Institute, University of Groningen, Groningen, the Netherlands
- Corresponding author
- Poolman, Bert
- Venue
- Microbiology and Molecular Biology Reviews
- Publisher
- American Society for Microbiology
- Published
- 2024-06-27
- Volume
- 88
- Issue
- 2
- Pages
- e0018123-e0018123
- ISSN
- 1092-2172 (ISSN-L)
- 1098-5557
- PMC
- PMC11332354
- OpenAlex
- W4399495726
- Cited by
- 26
- References
- 4
- Citations by year
- 2026: 14 · 2025: 12
- FWCI
- 1.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Microbiology and Molecular Biology Reviews (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Funders
- NWO (BaSyC Gravitation program, OCENW.KLEIN.526)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- cyclic di-AMP, nucleotide second messengers, cell wall remodeling, DNA repair, sporulation, glycogen turnover, innate immune response, Firmicutes, actinobacteria, cyanobacteria
- MeSH terms
- Bacteria, Bacterial Proteins, Cell Wall, Dinucleoside Phosphates, Second Messenger Systems, Signal Transduction, Gene Expression Regulation, Bacterial
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