The second messenger c-di-AMP inhibits the osmolyte uptake system OpuC in Staphylococcus aureus
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The second messenger c-di-AMP binds to and inhibits a component of a transporter that helps bacterial cells adapt to osmotic stress.
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Increased c-di-AMP inhibits compatible solute uptake by the Opu-family proteins.
“Furthermore, increased c-di-AMP inhibits compatible solute uptake by the Opu-family proteins (35, 46).”
From A Central Role for Magnesium Homeostasis during Adaptation to Osmotic Stress (2022) · cites this paper as [35]
The Results report reduced carnitine uptake at early time points in a Staphylococcus aureus strain with elevated c-di-AMP, and the Discussion identifies OpuC as the relevant transporter. The paper does not establish inhibition across Opu-family proteins or compatible solutes generally; it says OpuC was the only osmoprotectant uptake system identified as a c-di-AMP target. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCyclic di-AMP has been implicated in growth under osmotic stress due to its central role in coordinating K+ homeostasis.
“Cyclic di-AMP has been implicated in growth under osmotic stress due to its central role in coordinating K+ homeostasis (26, 35, 36).”
From A Central Role for Magnesium Homeostasis during Adaptation to Osmotic Stress (2022) · cites this paper as [35]
The pgpH gdpP double mutant was not rescued by glycine betaine.
“Interestingly, and consistent with the established inhibition of compatible solute import by c-di-AMP (35, 39, 40), the pgpH gdpP double mutant was not rescued by GB (Fig. S4B).”
From A Central Role for Magnesium Homeostasis during Adaptation to Osmotic Stress (2022) · cites this paper as [35]
The citation supports the preceding background point about c-di-AMP inhibiting compatible-solute uptake, not the citing paper’s observation that its pgpH gdpP double mutant was not rescued by glycine betaine; that observation points to Fig. S4B. The source’s Results section reports reduced carnitine uptake in a ΔgdpP strain, but does not address glycine-betaine rescue of a pgpH gdpP double mutant. (LLM, conf=0.78)
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Gundlach, J., Herzberg, C., Kaever, V., Gunka, K., Hoffmann, T., Weiß, M., Gibhardt, J., Thürmer, A., Hertel, D., Daniel, R., et al. (2017) · Science Signaling · doi:10.1126/scisignal.aal3011 · Cited by 200 · see citing works
Pham, H. T., Nhiep, N. T. H., Vu, T. N. M., Huynh, T. N., Zhu, Y., Huynh, A. L. D., Chakrabortti, A., Marcellin, E., Lo, R., Howard, C. B., et al. (2018) · PLOS Genetics · doi:10.1371/journal.pgen.1007574 · Cited by 75 · see citing works
A Central Role for Magnesium Homeostasis during Adaptation to Osmotic Stress
Wendel, B. M., Pi, H., Krüger, L., Herzberg, C., Stülke, J., & Helmann, J. D. (2022) · mBio · doi:10.1128/mbio.00092-22 · Cited by 57 · see citing works
- Authors
- Schuster, C. F., Bellows, L. E., Tosi, T., Campeotto, I., Corrigan, R. M., Freemont, P., & Gründling, A.
- Affiliations
- Imperial College London (GB)
- Corresponding author
- Schuster, Christopher F.
- Bellows, Lauren E.
- Gründling, Angelika
- ORCID
- Venue
- Science Signaling
- Published
- 2016-08-16
- Volume
- 9
- Issue
- 441
- Pages
- ra81-ra81
- ISSN
- 1937-9145 (ISSN-L)
- 1945-0877
- PMC
- PMC5248971
- OpenAlex
- W2507323902
- Cited by
- 109
- References
- 0
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 13 · 2023: 17 · 2022: 10 · 2021: 8 · 2020: 15 · 2019: 14 · 2018: 7 · 2017: 9 · 2016: 3
- FWCI
- 8.89
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science Signaling (publishedVersion)
- PubMed (publishedVersion)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Nottingham Trent University's Institutional Repository (Nottingham Trent Repository) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- European Research Council (260371)
- Wellcome Trust (100289)
- Deutsche Forschungsgemeinschaft (DFG) (SCHU 3159/1-1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Health Sciences › Medicine › Infectious Diseases › Antimicrobial Resistance in Staphylococcus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- c-di-AMP, Staphylococcus aureus, osmotic stress, osmolytes, carnitine uptake, potassium uptake, second messenger signaling, ATPase, CBS domain, protein inhibition, crystal structure
- MeSH terms
- Protein Domains, Bacterial Proteins, Carnitine, Osmotic Pressure, Staphylococcus aureus, Dinucleoside Phosphates, Second Messenger Systems, Crystallography, X-Ray, ATP-Binding Cassette Transporters
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