{"doi":"10.1101/2024.04.17.589803","title":"Prophage-encoded methyltransferase drives adaptation of community-acquired methicillin-resistant <i>Staphylococcus aureus</i>","abstract":"Abstract We recently described the evolution of a community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 variant responsible for an outbreak of skin and soft tissue infections. Acquisition of a mosaic version of the Φ11 prophage (mΦ11) that increases skin abscess size was an early step in CA-MRSA adaptation that primed the successful spread of the clone. The present report shows how prophage mΦ11 exerts its effect on virulence for skin infection without encoding a known toxin or fitness genes. Abscess size and skin inflammation were associated with DNA methylase activity of an mΦ11-encoded adenine methyltransferase (designated pamA ). pamA increased expression of fibronectin-binding protein A ( fnbA ; FnBPA), and inactivation of fnbA eliminated the effect of pamA on abscess virulence without affecting strains lacking pamA . Thus, fnbA is a pamA -specific virulence factor. Mechanistically, pamA was shown to promote biofilm formation in vivo in skin abscesses, a phenotype linked to FnBPA’s role in biofilm formation. Collectively, these data reveal a novel mechanism—epigenetic regulation of staphylococcal gene expression—by which phage can regulate virulence to drive adaptive leaps by S. aureus . Graphical Abstract","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":486960,"datarank":0.2172961399374432,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.00935198576945958,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.00935198576945958,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":3,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9487,"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":985691,"name":"Magdalena Podkowik","orcid":"0000-0002-6095-4741","position":1,"is_corresponding":false},{"id":1227600,"name":"Rebecca Tierce","orcid":"0009-0006-5208-0761","position":2,"is_corresponding":false},{"id":1331025,"name":"Irnov Irnov","orcid":"0000-0001-8631-4075","position":3,"is_corresponding":false},{"id":72622,"name":"Gregory Putzel","orcid":"0000-0002-5211-2608","position":4,"is_corresponding":false},{"id":1008836,"name":"Nora M. Samhadaneh","orcid":null,"position":5,"is_corresponding":false},{"id":478774,"name":"Keenan A. Lacey","orcid":"0000-0002-9242-0170","position":6,"is_corresponding":false},{"id":1033729,"name":"Daiane Boff","orcid":"0000-0001-8127-916X","position":7,"is_corresponding":false},{"id":1327308,"name":"Sabrina M. Morales","orcid":null,"position":8,"is_corresponding":false},{"id":1056182,"name":"Sohei Makita","orcid":"0000-0001-9752-4385","position":9,"is_corresponding":false},{"id":1040413,"name":"Theodora K. Karagounis","orcid":"0000-0003-1481-9589","position":10,"is_corresponding":false},{"id":345071,"name":"Erin E. Zwack","orcid":"0000-0003-4729-8468","position":11,"is_corresponding":false},{"id":393123,"name":"Chunyi Zhou","orcid":"0000-0003-1278-5901","position":12,"is_corresponding":false},{"id":666075,"name":"Randie H. Kim","orcid":"0000-0003-0365-5961","position":13,"is_corresponding":false},{"id":311840,"name":"Karl Drlica","orcid":"0000-0002-4831-6384","position":14,"is_corresponding":false},{"id":233295,"name":"Alejandro Pironti","orcid":"0000-0002-7759-6776","position":15,"is_corresponding":false},{"id":21492,"name":"Harm van Bakel","orcid":"0000-0002-1376-6916","position":16,"is_corresponding":false},{"id":308670,"name":"Victor J. Torres","orcid":"0000-0002-7126-0489","position":17,"is_corresponding":false},{"id":253553,"name":"Bo Shopsin","orcid":"0009-0001-7729-8584","position":18,"is_corresponding":false},{"id":3910,"name":"Robert J. Ulrich","orcid":"0000-0002-3217-5062","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:08:06.013846Z","pmid":"38659881","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":[]}