{"doi":"10.1093/jac/dkae455","title":"NaHCO3 modulates the <i>bla</i> operon and β-lactam susceptibility in borderline oxacillin-resistant <i>Staphylococcus aureus</i> (BORSA)","abstract":"BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) are resistant to nearly all β-lactam antibiotics under standard testing conditions. However, a novel phenotype exists wherein certain MRSA strains exhibit β-lactam susceptibility in the presence of bicarbonate (termed 'NaHCO3-responsive'), an abundant ion in mammalian tissues and blood. This suggests that specific MRSA infections may be treatable by β-lactams. NaHCO3 responsiveness appears due to effects of NaHCO3 on the expression mecA/PBP2a and other accessory genes required for PBP functionality. mecA expression can be co-regulated by the bla operon regulatory genes, blaI and blaR1. OBJECTIVES: To elucidate the influence of NaHCO3 specifically on the bla operon via investigations of the impact of NaHCO3 on β-lactamase hyper-producing, mecA-negative, borderline oxacillin-resistant Staphylococcus aureus (BORSA) strains. METHODS: Evaluate the effect of NaHCO3 on β-lactam susceptibility via minimum inhibitory concentrations (MIC) assay, expression of genes within the bla operon (blaZ, blaI, blaR1) via RT-qPCR, and β-lactamase (BlaZ) activity via nitrocefinase assay in BORSA. RESULTS: NaHCO3 enhanced susceptibility to β-lactamase-susceptible β-lactams penicillin and ampicillin. NaHCO3 had no impact on susceptibility to the anti-staphylococcal β-lactams oxacillin and cefazolin, or the anti-MRSA antibiotics vancomycin and daptomycin. NaHCO3 repressed expression of all genes within the bla operon and reduced β-lactamase production. CONCLUSIONS: These data demonstrate that NaHCO3 influences expression of genes within the bla operon, translating to reduced β-lactamase production and enhanced β-lactam susceptibility in BORSA strains. Furthermore, this indicates that the classical blaZ regulators, blaI and blaR1, are the likely mediators of NaHCO3-mediated repression of mecA. However, questions still remain regarding the mechanism via which NaHCO3 regulates the bla operon.","journal":"Journal of Antimicrobial Chemotherapy","year":2024,"id":461783,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"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":1282872,"name":"Sabrina L. Madrigal","orcid":null,"position":1,"is_corresponding":false},{"id":397629,"name":"Richard A. Proctor","orcid":"0000-0003-3011-7958","position":2,"is_corresponding":false},{"id":232760,"name":"Henry F. Chambers","orcid":"0000-0001-5317-4491","position":3,"is_corresponding":false},{"id":397630,"name":"Yan Q. Xiong","orcid":"0000-0002-8732-6948","position":4,"is_corresponding":false},{"id":397631,"name":"Arnold S. Bayer","orcid":"0000-0003-1968-0192","position":5,"is_corresponding":false},{"id":397628,"name":"Selvi C. Ersoy","orcid":"0000-0002-8792-2061","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-19T02:04:16.410510Z","pmid":"39704154","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":[]}