{"doi":"10.3389/fcimb.2024.1418651","title":"The multifaceted role of c-di-AMP signaling in the regulation of Porphyromonas gingivalis lipopolysaccharide structure and function","abstract":"Background This study unveils the intricate functional association between cyclic di-3’,5’-adenylic acid (c-di-AMP) signaling, cellular bioenergetics, and the regulation of lipopolysaccharide (LPS) profile in Porphyromonas gingivalis , a Gram-negative obligate anaerobe considered as a keystone pathogen involved in the pathogenesis of chronic periodontitis. Previous research has identified variations in P. gingivalis LPS profile as a major virulence factor, yet the underlying mechanism of its modulation has remained elusive. Methods We employed a comprehensive methodological approach, combining two mutants exhibiting varying levels of c-di-AMP compared to the wild type, alongside an optimized analytical methodology that combines conventional mass spectrometry techniques with a novel approach known as FLAT n . Results We demonstrate that c-di-AMP acts as a metabolic nexus, connecting bioenergetic status to nuanced shifts in fatty acid and glycosyl profiles within P. gingivalis LPS. Notably, the predicted regulator gene cdaR , serving as a potent regulator of c-di-AMP synthesis, was found essential for producing N-acetylgalactosamine and an unidentified glycolipid class associated with the LPS profile. Conclusion The multifaceted roles of c-di-AMP in bacterial physiology are underscored, emphasizing its significance in orchestrating adaptive responses to stimuli. Furthermore, our findings illuminate the significance of LPS variations and c-di-AMP signaling in determining the biological activities and immunostimulatory potential of P. gingivalis LPS, promoting a pathoadaptive strategy. The study expands the understanding of c-di-AMP pathways in Gram-negative species, laying a foundation for future investigations into the mechanisms governing variations in LPS structure at the molecular level and their implications for host-pathogen interactions.","journal":"Frontiers in Cellular and Infection Microbiology","year":2024,"id":480381,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9506,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":764627,"name":"Artur Muszyński","orcid":"0000-0003-3497-9977","position":1,"is_corresponding":false},{"id":363565,"name":"Hyojik Yang","orcid":"0000-0002-1659-2771","position":2,"is_corresponding":false},{"id":371311,"name":"Ratnam S. Seelan","orcid":"0000-0002-8925-1070","position":3,"is_corresponding":false},{"id":1319974,"name":"Asal Mohammadi","orcid":null,"position":4,"is_corresponding":false},{"id":1319975,"name":"Jacob S. Hilson","orcid":null,"position":5,"is_corresponding":false},{"id":1194924,"name":"Griffin Keiser","orcid":"0009-0008-1596-6605","position":6,"is_corresponding":false},{"id":490135,"name":"Frank C. Nichols","orcid":"0000-0001-6800-1112","position":7,"is_corresponding":false},{"id":91961,"name":"Parastoo Azadi","orcid":"0000-0002-6166-9432","position":8,"is_corresponding":false},{"id":301698,"name":"Robert K. Ernst","orcid":"0000-0001-5016-8694","position":9,"is_corresponding":false},{"id":1319976,"name":"Fata Moradali","orcid":null,"position":10,"is_corresponding":false},{"id":773116,"name":"Shirin Ghods","orcid":null,"position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-19T02:06:58.305365Z","pmid":"38933693","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":[]}