{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T06:09:54Z","timestamp":1780553394779,"version":"3.54.1"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1RO1-AI146078"],"award-info":[{"award-number":["1RO1-AI146078"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Methicillin-resistant Staphylococcus aureus (MRSA) are resistant to nearly all \u03b2-lactam antibiotics under standard testing conditions. However, a novel phenotype exists wherein certain MRSA strains exhibit \u03b2-lactam susceptibility in the presence of bicarbonate (termed \u2018NaHCO3-responsive\u2019), an abundant ion in mammalian tissues and blood. This suggests that specific MRSA infections may be treatable by \u03b2-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.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To elucidate the influence of NaHCO3 specifically on the bla operon via investigations of the impact of NaHCO3 on \u03b2-lactamase hyper-producing, mecA-negative, borderline oxacillin-resistant Staphylococcus aureus (BORSA) strains.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Evaluate the effect of NaHCO3 on \u03b2-lactam susceptibility via minimum inhibitory concentrations (MIC) assay, expression of genes within the bla operon (blaZ, blaI, blaR1) via RT\u2013qPCR, and \u03b2-lactamase (BlaZ) activity via nitrocefinase assay in BORSA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>NaHCO3 enhanced susceptibility to \u03b2-lactamase-susceptible \u03b2-lactams penicillin and ampicillin. NaHCO3 had no impact on susceptibility to the anti-staphylococcal \u03b2-lactams oxacillin and cefazolin, or the anti-MRSA antibiotics vancomycin and daptomycin. NaHCO3 repressed expression of all genes within the bla operon and reduced \u03b2-lactamase production.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These data demonstrate that NaHCO3 influences expression of genes within the bla operon, translating to reduced \u03b2-lactamase production and enhanced \u03b2-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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae455","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T10:57:42Z","timestamp":1734692262000},"page":"676-681","source":"Crossref","is-referenced-by-count":3,"title":["NaHCO3 modulates the <i>bla<\/i> operon and \u03b2-lactam susceptibility in borderline oxacillin-resistant <i>Staphylococcus aureus<\/i> (BORSA)"],"prefix":"10.1093","volume":"80","author":[{"given":"Selvi C","family":"Ersoy","sequence":"first","affiliation":[{"name":"Division of Infection Disease, The Lundquist Institute at Harbor-UCLA Medical Center , Torrance, CA ,","place":["USA"]},{"name":"David Geffen School of Medicine at UCLA , Los Angeles, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina L","family":"Madrigal","sequence":"additional","affiliation":[{"name":"Department of 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