{"doi":"10.1111/mmi.70003","title":"Cyclic Di‐<scp>AMP</scp> Affects Cell Membrane Integrity of <i>Streptococcus pneumoniae</i>","abstract":"ABSTRACT Competence is an important bioprocess for Streptococcus pneumoniae . Previously, we demonstrated that the bacterial second messenger cyclic di‐adenosine monophosphate (c‐di‐AMP) modulates pneumococcal competence. Surprisingly, cdaA* , a strain producing less c‐di‐AMP due to a point mutation in the diadenylate cyclase CdaA, is susceptible to competence‐stimulating peptide (CSP). In this study, we screened cdaA * suppressor mutants resistant to CSP to explore the underlying mechanism. Of 14 clones sequenced, nine clones possessed mutations in the c‐di‐AMP phosphodiesterase Pde1, indicating that the susceptibility to CSP of the cdaA * strain is correlated to c‐di‐AMP levels. Another two clones exhibited a mutation in FabT, a transcription factor controlling cell membrane fatty acid biosynthesis. We further showed that deletion of fabT , disruption of the FabT‐binding site within the P fabK promoter, deletion of a fabT activator BriC, or disruption of K + uptake in the cdaA * mutant all rescued the growth defect of the cdaA * strain in media supplemented with CSP. Finally, we found that a c‐di‐AMP phosphodiesterase‐null mutant with high levels of c‐di‐AMP is highly sensitive to treatment with either ethanol or Triton X‐100, which could be corrected by reducing c‐di‐AMP levels through introducing point mutations in CdaA. Together, these findings indicate that c‐di‐AMP affects cell membrane integrity.","journal":"Molecular Microbiology","year":2025,"id":569281,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1356826,"name":"Jianle Gao","orcid":null,"position":1,"is_corresponding":false},{"id":1356827,"name":"Nathan Forrest","orcid":null,"position":2,"is_corresponding":false},{"id":1356828,"name":"Elijah Crosbourne","orcid":null,"position":3,"is_corresponding":false},{"id":1356829,"name":"Kaibo Cui","orcid":null,"position":4,"is_corresponding":false},{"id":322527,"name":"Guangchun Bai","orcid":"0000-0002-2086-4020","position":5,"is_corresponding":false},{"id":322526,"name":"Tiffany M. Zarrella","orcid":"0000-0002-3053-4025","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T02:56:59.652443Z","pmid":"40576446","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":[]}