{"doi":"10.1073/pnas.2402764121","title":"Type VII secretion system extracellular protein B targets STING to evade host anti– <i>Staphylococcus aureus</i> immunity","abstract":"Staphylococcus aureus ( S. aureus ) can evade antibiotics and host immune defenses by persisting within infected cells. Here, we demonstrate that in infected host cells, S. aureus type VII secretion system (T7SS) extracellular protein B (EsxB) interacts with the stimulator of interferon genes (STING) protein and suppresses the inflammatory defense mechanism of macrophages during early infection. The binding of EsxB with STING disrupts the K48-linked ubiquitination of EsxB at lysine 33, thereby preventing EsxB degradation. Furthermore, EsxB-STING binding appears to interrupt the interaction of 2 vital regulatory proteins with STING: aspartate-histidine-histidine-cysteine domain-containing protein 3 (DHHC3) and TNF receptor-associated factor 6. This persistent dual suppression of STING interactions deregulates intracellular proinflammatory pathways in macrophages, inhibiting STING’s palmitoylation at cysteine 91 and its K63-linked ubiquitination at lysine 83. These findings uncover an immune-evasion mechanism by S. aureus T7SS during intracellular macrophage infection, which has implications for developing effective immunomodulators to combat S. aureus infections.","journal":"Proceedings of the National Academy of Sciences","year":2024,"id":426006,"datarank":0.4493598410330987,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.0,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"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":502585,"name":"Tian Tian","orcid":"0000-0001-6317-943X","position":1,"is_corresponding":false},{"id":892271,"name":"Tingrong Xiong","orcid":null,"position":2,"is_corresponding":false},{"id":970144,"name":"Xiaomei Zhang","orcid":"0009-0000-5875-4284","position":3,"is_corresponding":false},{"id":397263,"name":"Xiaomei Zhang","orcid":"0000-0003-0964-8922","position":4,"is_corresponding":false},{"id":228251,"name":"Ning Wang","orcid":"0000-0003-1410-329X","position":5,"is_corresponding":false},{"id":891579,"name":"Luxuan Liu","orcid":"0009-0001-3688-9230","position":6,"is_corresponding":false},{"id":891581,"name":"Yun Shi","orcid":"0000-0003-1925-4337","position":7,"is_corresponding":false},{"id":1224817,"name":"Qiang Liu","orcid":"0000-0002-6343-8080","position":8,"is_corresponding":false},{"id":892272,"name":"Dongshui Lu","orcid":null,"position":9,"is_corresponding":false},{"id":1224818,"name":"Ping Luo","orcid":"0000-0001-9396-1932","position":10,"is_corresponding":false},{"id":1224819,"name":"Weijun Zhang","orcid":"0009-0006-1540-7382","position":11,"is_corresponding":false},{"id":892273,"name":"Ping Cheng","orcid":null,"position":12,"is_corresponding":false},{"id":892274,"name":"Qiang Gou","orcid":null,"position":13,"is_corresponding":false},{"id":1224820,"name":"Yu Wang","orcid":"0000-0001-7894-6523","position":14,"is_corresponding":false},{"id":891585,"name":"Hao Zeng","orcid":"0000-0002-2061-6350","position":15,"is_corresponding":false},{"id":891577,"name":"Xiaokai Zhang","orcid":"0000-0003-2878-2385","position":16,"is_corresponding":false},{"id":427301,"name":"Quanming Zou","orcid":null,"position":18,"is_corresponding":false},{"id":1224816,"name":"Lin Gao","orcid":"0000-0002-1021-8148","position":0,"is_corresponding":true}],"reference_count":38,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:58:37.924718Z","pmid":"38771879","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":[]}