ArticlePLoS genetics2018
Cyclic di-AMP regulation of osmotic homeostasis is essential in Group B Streptococcus.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 87 citations in OpenAlex.
- Article
- Cyclic di-adenosine monophosphate as a potential regulator of sporulation and solventogenesis in Clostridium beijerinckii: a hypothesis.World journal of microbiology & biotechnology · 2026Review
- TrkA ofMicrobiology (Reading, England) · 2025Article
- Cyclic-di-AMP modulates cellular turgor in response to defects in bacterial cell wall synthesis.Nature microbiology · 2025Article
- Biofilm formation byProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Bacterial cell volume regulation and the importance of cyclic di-AMP.Microbiology and molecular biology reviews : MMBR · 2024Review
- The serine-rich repeat glycoprotein Srr2 mediates Streptococcus agalactiae interaction with host fibronectin.BMC microbiology · 2024Article
- Allosteric regulation by c-di-AMP modulates a complete N-acetylglucosamine signaling cascade in Saccharopolyspora erythraea.Nature communications · 2024Article
- Coordinated regulation of osmotic imbalance by c-di-AMP shapes ß-lactam tolerance in Group BmicroLife · 2024Article
- The Many Ways to Deal with STING.International journal of molecular sciences · 2023Review
- Recent advances and perspectives in nucleotide second messenger signaling in bacteria.microLife · 2023Review
- The many roles of cyclic di-AMP to control the physiology ofmicroLife · 2023Review
- Cyclic di-AMP, a multifaceted regulator of central metabolism and osmolyte homeostasis inmicroLife · 2023Review
- Redundant potassium transporter systems guarantee the survival ofFrontiers in microbiology · 2023Article
- FabT, a Bacterial Transcriptional Repressor That Limits Futile Fatty Acid Biosynthesis.Microbiology and molecular biology reviews : MMBR · 2022Review
- c-di-AMP signaling is required for bile salt resistance, osmotolerance, and long-term host colonization byScience signaling · 2022Article
- Atypical cyclic di-AMP signaling is essential for Porphyromonas gingivalis growth and regulation of cell envelope homeostasis and virulence.NPJ biofilms and microbiomes · 2022Article
- Listeria monocytogenes exposed to antimicrobial peptides displays differential regulation of lipids and proteins associated to stress response.Cellular and molecular life sciences : CMLS · 2022Article
- The role of bacterial cyclic di-adenosine monophosphate in the host immune response.Frontiers in microbiology · 2022Review
- BusR senses bipartite DNA binding motifs by a unique molecular ruler architecture.Nucleic acids research · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclic nucleotides are universally used as secondary messengers to control cellular physiology. Among these signalling molecules, cyclic di-adenosine monophosphate (c-di-AMP) is a specific bacterial second messenger recognized by host cells during infections and its synthesis is assumed to be necessary for bacterial growth by controlling a conserved and essential cellular function. In this study, we sought to identify the main c-di-AMP dependent pathway in Streptococcus agalactiae, the etiological agent of neonatal septicaemia and meningitis. By conditionally inactivating dacA, the only diadenyate cyclase gene, we confirm that c-di-AMP synthesis is essential in standard growth conditions. However, c-di-AMP synthesis becomes rapidly dispensable due to the accumulation of compensatory mutations. We identified several mutations restoring the viability of a ΔdacA mutant, in particular a loss-of-function mutation in the osmoprotectant transporter BusAB. Identification of c-di-AMP binding proteins revealed a conserved set of potassium and osmolyte transporters, as well as the BusR transcriptional factor. We showed that BusR negatively regulates busAB transcription by direct binding to the busAB promoter. Loss of BusR repression leads to a toxic busAB expression in absence of c-di-AMP if osmoprotectants, such as glycine betaine, are present in the medium. In contrast, deletion of the gdpP c-di-AMP phosphodiesterase leads to hyperosmotic susceptibility, a phenotype dependent on a functional BusR. Taken together, we demonstrate that c-di-AMP is essential for osmotic homeostasis and that the predominant mechanism is dependent on the c-di-AMP binding transcriptional factor BusR. The regulation of osmotic homeostasis is likely the conserved and essential function of c-di-AMP, but each species has evolved specific c-di-AMP mechanisms of osmoregulation to adapt to its environment.
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