{"doi":"10.1093/femsre/fuaa019","title":"A decade of research on the second messenger c-di-AMP","abstract":"Cyclic dimeric adenosine 3',5'-monophosphate (c-di-AMP) is an emerging second messenger in bacteria and archaea that is synthesized from two molecules of ATP by diadenylate cyclases and degraded to pApA or two AMP molecules by c-di-AMP-specific phosphodiesterases. Through binding to specific protein- and riboswitch-type receptors, c-di-AMP regulates a wide variety of prokaryotic physiological functions, including maintaining the osmotic pressure, balancing central metabolism, monitoring DNA damage and controlling biofilm formation and sporulation. It mediates bacterial adaptation to a variety of environmental parameters and can also induce an immune response in host animal cells. In this review, we discuss the phylogenetic distribution of c-di-AMP-related enzymes and receptors and provide some insights into the various aspects of c-di-AMP signaling pathways based on more than a decade of research. We emphasize the key role of c-di-AMP in maintaining bacterial osmotic balance, especially in Gram-positive bacteria. In addition, we discuss the future direction and trends of c-di-AMP regulatory network, such as the likely existence of potential c-di-AMP transporter(s), the possibility of crosstalk between c-di-AMP signaling with other regulatory systems, and the effects of c-di-AMP compartmentalization. This review aims to cover the broad spectrum of research on the regulatory functions of c-di-AMP and c-di-AMP signaling pathways.","journal":"FEMS Microbiology Reviews","year":2020,"id":53359,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":118,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9528,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":271882,"name":"Xia Cai","orcid":"0000-0001-8428-2487","position":1,"is_corresponding":false},{"id":273138,"name":"Hongdan Ma","orcid":null,"position":2,"is_corresponding":false},{"id":271883,"name":"Li Zhu","orcid":"0000-0002-8586-7249","position":3,"is_corresponding":false},{"id":271884,"name":"Yuling Zhang","orcid":"0000-0002-8319-8387","position":4,"is_corresponding":false},{"id":271885,"name":"Shan‐Ho Chou","orcid":"0000-0002-5202-8238","position":5,"is_corresponding":false},{"id":11690,"name":"Michael Y. Galperin","orcid":"0000-0002-2265-5572","position":6,"is_corresponding":false},{"id":271886,"name":"Jin He","orcid":"0000-0002-1456-8284","position":7,"is_corresponding":false},{"id":271881,"name":"Wen Yin","orcid":"0000-0002-4734-9483","position":0,"is_corresponding":true}],"reference_count":138,"raw_metadata":null,"created_at":"2026-07-18T20:44:25.349797Z","pmid":"32472931","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}