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A phenotype termed \u201cNaHCO\n              <jats:sub>3<\/jats:sub>\n              -responsiveness\u201d has been identified, wherein many clinical MRSA isolates are rendered susceptible to standard-of-care \u03b2-lactams in the presence of physiologically relevant concentrations of NaHCO\n              <jats:sub>3<\/jats:sub>\n              ,\n              <jats:italic>in vitro<\/jats:italic>\n              and\n              <jats:italic>ex vivo<\/jats:italic>\n              ; moreover, such \u201cNaHCO\n              <jats:sub>3<\/jats:sub>\n              -responsive\u201d isolates can be effectively cleared by \u03b2-lactams from target tissues in experimental infective endocarditis (IE). One mechanistic impact of NaHCO\n              <jats:sub>3<\/jats:sub>\n              exposure on NaHCO\n              <jats:sub>3<\/jats:sub>\n              -responsive MRSA is to repress WTA synthesis. This NaHCO\n              <jats:sub>3<\/jats:sub>\n              effect mimics the phenotype of\n              <jats:italic>tarO<\/jats:italic>\n              -deficient MRSA, including sensitization to the PBP2-targeting \u03b2-lactam, cefuroxime (CFX). Herein, we further investigated the impacts of NaHCO\n              <jats:sub>3<\/jats:sub>\n              exposure on CFX susceptibility in the presence and absence of a WTA synthesis inhibitor, ticlopidine (TCP), in a collection of clinical MRSA isolates from skin and soft tissue infections (SSTI) and bloodstream infections (BSI). NaHCO\n              <jats:sub>3<\/jats:sub>\n              and\/or TCP enhanced susceptibility to CFX\n              <jats:italic>in vitro<\/jats:italic>\n              , by both minimum inhibitor concentration (MIC) and time-kill assays, as well as in an\n              <jats:italic>ex vivo<\/jats:italic>\n              simulated endocarditis vegetations (SEV) model, in NaHCO\n              <jats:sub>3<\/jats:sub>\n              -responsive MRSA. Furthermore, in experimental IE (presumably in the presence of endogenous NaHCO\n              <jats:sub>3<\/jats:sub>\n              ), pre-exposure to TCP prior to infection sensitized the NaHCO\n              <jats:sub>3<\/jats:sub>\n              -responsive MRSA strain (but not the non-responsive strain) to enhanced clearances by CFX in target tissues. These data support the notion that NaHCO\n              <jats:sub>3<\/jats:sub>\n              is acting similarly to WTA synthesis inhibitors, and that such inhibitors have potential translational applications in the treatment of certain MRSA strains in conjunction with specific \u03b2-lactam agents.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01627-23","type":"journal-article","created":{"date-parts":[[2024,2,13]],"date-time":"2024-02-13T14:01:29Z","timestamp":1707832889000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Sensitizing methicillin-resistant\n            <i>Staphylococcus aureus<\/i>\n            (MRSA) to cefuroxime: the synergic effect of bicarbonate and the wall teichoic acid inhibitor ticlopidine"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8792-2061","authenticated-orcid":true,"given":"Selvi C.","family":"Ersoy","sequence":"first","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovations at Harbor-UCLA Medical Center, Torrance, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A.","family":"Proctor","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA"},{"name":"Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5012-5993","authenticated-orcid":true,"given":"Warren E.","family":"Rose","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wessam","family":"Abdelhady","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovations at Harbor-UCLA Medical Center, Torrance, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0556-238X","authenticated-orcid":true,"given":"Sook-Ha","family":"Fan","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovations at Harbor-UCLA Medical Center, Torrance, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina L.","family":"Madrigal","sequence":"additional","affiliation":[{"name":"California State University-Los Angeles, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed M.","family":"Elsayed","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovations at Harbor-UCLA Medical Center, Torrance, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry F.","family":"Chambers","sequence":"additional","affiliation":[{"name":"University of California-San Francisco School of Medicine, San Francisco, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4533-7531","authenticated-orcid":true,"given":"Rita G.","family":"Sobral","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Microbiology of Bacterial Pathogens, UCIBIO, Applied Molecular Biosciences Unit, Department of Life Sciences, Nova School of Science and Technology, Universidade Nova de Lisboa, Caparica, Portugal"},{"name":"Associate Laboratory i4HB, Institute for Health and Bioeconomy, Nova School of Science and Technology, Universidade Nova de Lisboa, Caparica, Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnold S.","family":"Bayer","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovations at Harbor-UCLA Medical Center, Torrance, California, USA"},{"name":"David Geffen School of Medicine at UCLA, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/653519"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2016.07.010"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.2165\/00019053-200725090-00004"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00496-19"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02445-19"},{"key":"e_1_3_3_7_2","volume-title":"Clin microbiol infect in revision","author":"Ersoy SC","year":"2023","unstructured":"Ersoy SC, Madrigal SL, Proctor RA, Chen L, MediavillaJR, Kreiswirth BN, Flores EA, Miller LG, PatelR, Chambers HF, Bayer AS. 2023. 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