{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T00:40:19Z","timestamp":1788914419015,"version":"build-2803163510"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T00:00:00Z","timestamp":1706659200000},"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":["R01 AI139244"],"award-info":[{"award-number":["R01 AI139244"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-168842"],"award-info":[{"award-number":["PJT-168842"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Staphylococcus aureus is the most common cause of life-threatening endovascular infections, including infective endocarditis (IE). These infections, especially when caused by methicillin-resistant strains (MRSA), feature limited therapeutic options and high morbidity and mortality rates.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Herein, we investigated the role of the purine biosynthesis repressor, PurR, in virulence factor expression and vancomycin (VAN) treatment outcomes in experimental IE due to MRSA.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The PurR-mediated repression of purine biosynthesis was confirmed by enhanced purF expression and production of an intermediate purine metabolite in purR mutant strain. In addition, enhanced expression of the transcriptional regulators, sigB and sarA, and their key downstream virulence genes (eg, fnbA, and hla) was demonstrated in the purR mutant in vitro and within infected cardiac vegetations. Furthermore, purR deficiency enhanced fnbA\/fnbB transcription, translating to increased fibronectin adhesion versus the wild type and purR-complemented strains. Notably, the purR mutant was refractory to significant reduction in target tissues MRSA burden following VAN treatment in the IE model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These findings suggest that the purine biosynthetic pathway intersects the coordination of virulence factor expression and in vivo persistence during VAN treatment, and may represent an avenue for novel antimicrobial development targeting MRSA.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiad577","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T06:58:13Z","timestamp":1706770693000},"page":"1648-1657","source":"Crossref","is-referenced-by-count":16,"title":["The Purine Biosynthesis Repressor, PurR, Contributes to Vancomycin Susceptibility of Methicillin-resistant <i>Staphylococcus aureus<\/i> in Experimental Endocarditis"],"prefix":"10.1093","volume":"229","author":[{"given":"Yan Q","family":"Xiong","sequence":"first","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation, Harbor-University of California Los Angeles Medical Center , Torrance, California , USA"},{"name":"Department of Medicine, Division of Infectious Diseases, Harbor-University of California Los Angeles Medical Center , Torrance, California , USA"},{"name":"David Geffen School of Medicine, University of California Los Angeles , Los Angeles, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Li","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation, Harbor-University of California Los Angeles Medical Center , Torrance, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariya I","family":"Goncheva","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Western Ontario , London, Ontario , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M","family":"Elsayed","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation, Harbor-University of California Los Angeles Medical Center , Torrance, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengli","family":"Zhu","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation, Harbor-University of California Los Angeles Medical Center , Torrance, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Li","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation, Harbor-University of California Los Angeles Medical Center , Torrance, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wessam","family":"Abdelhady","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation, Harbor-University of California Los Angeles Medical Center , Torrance, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald S","family":"Flannagan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Western Ontario , London, Ontario , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R","family":"Yeaman","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation, Harbor-University of California Los Angeles Medical Center , Torrance, California , USA"},{"name":"Department of Medicine, Division of Infectious Diseases, Harbor-University of California Los Angeles Medical Center , Torrance, California , USA"},{"name":"David Geffen School of Medicine, University of California Los Angeles , Los Angeles, California , USA"},{"name":"Department of Medicine, Division of Molecular Medicine, Harbor-University of California Los Angeles Medical Center , Torrance, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold S","family":"Bayer","sequence":"additional","affiliation":[{"name":"The Lundquist Institute for Biomedical Innovation, Harbor-University of California Los Angeles Medical Center , Torrance, California , USA"},{"name":"Department of Medicine, Division of Infectious Diseases, Harbor-University of California Los Angeles Medical Center , Torrance, California , USA"},{"name":"David Geffen School of Medicine, University of California Los Angeles , Los Angeles, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E","family":"Heinrichs","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Western Ontario , 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