{"doi":"10.1093/infdis/jiae640","title":"Phage-Encoded Virulence Factor, Gp05, Alters Membrane Phospholipids and Reduces Antimicrobial Susceptibility in Methicillin-Resistant <i>Staphylococcus aureus</i>","abstract":"BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of endovascular infections. The prophage-encoded protein Gp05 has been identified as a critical virulence factor that contributes to MRSA persistence during vancomycin treatment in an experimental endocarditis model. However, the mechanisms underlying this persistence phenotype remain poorly understood. METHODS: This study investigated the genetic factors contributing to Gp05-associated MRSA persistence utilizing RNA sequencing (RNA-seq) on an isogenic MRSA strain set, including a clinical persistent bacteremia isolate, its chromosomal gp05 deletion mutant, and gp05-complemented strains. RESULTS: RNA-seq revealed significant downregulation of the GraSR two-component regulatory system and its downstream genes, mprF and dltABCD, in the gp05 deletion mutant compared to the wild-type and gp05-complemented strains. This downregulation led to a substantial shift in membrane phospholipid composition, with an increased phosphatidylglycerol and a corresponding decrease in lysyl-phosphatidylglycerol. These changes resulted in increased susceptibility of the gp05 deletion mutant to human cationic antimicrobial peptide (CAMP) LL-37, neutrophils, and vancomycin. These results were confirmed in an isogenic gp05 overexpression strain set in MRSA JE2 background. CONCLUSIONS: Gp05 modulates MRSA surface phospholipid components and charge, offering new insights into the molecular mechanisms underlying Gp05-mediated persistence in endovascular infections and potential therapeutic targets to combat these infections.","journal":"The Journal of Infectious Diseases","year":2024,"id":472884,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9625,"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":447480,"name":"Nagendra N. Mishra","orcid":"0000-0002-7475-5794","position":1,"is_corresponding":false},{"id":231557,"name":"Liang Chen","orcid":"0000-0001-5845-2235","position":2,"is_corresponding":false},{"id":897436,"name":"Adhar C. Manna","orcid":"0000-0002-4055-2489","position":3,"is_corresponding":false},{"id":502764,"name":"Ambrose L. Cheung","orcid":"0000-0001-5120-3949","position":4,"is_corresponding":false},{"id":397629,"name":"Richard A. Proctor","orcid":"0000-0003-3011-7958","position":5,"is_corresponding":false},{"id":397630,"name":"Yan Q. Xiong","orcid":"0000-0002-8732-6948","position":6,"is_corresponding":false},{"id":963514,"name":"Yi Li","orcid":"0000-0002-5849-6040","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T02:05:57.032095Z","pmid":"39739874","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":[]}