{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:08:50Z","timestamp":1790518130502,"version":"4.1.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2020,4,25]],"date-time":"2020-04-25T00:00:00Z","timestamp":1587772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"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\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI130056"],"award-info":[{"award-number":["R01 AI130056"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01 AI124319"],"award-info":[{"award-number":["U01 AI124319"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Persistent methicillin-resistant Staphylococcus aureus (MRSA) endovascular infections represent a significant clinical-therapeutic challenge. Of particular concern is antibiotic treatment failure in infections caused by MRSA that are \u201csusceptible\u201d to antibiotic in vitro. In the current study, we investigate specific purine biosynthetic pathways and stringent response mechanism(s) related to this life-threatening syndrome using genetic matched persistent and resolving MRSA clinical bacteremia isolates (PB and RB, respectively), and isogenic MRSA strain sets. We demonstrate that PB isolates (vs RB isolates) have significantly higher (p)ppGpp production, phenol-soluble-modulin expression, polymorphonuclear leukocyte lysis and survival, fibronectin\/endothelial cell (EC) adherence, and EC damage. Importantly, an isogenic strain set, including JE2 parental, relP-mutant and relP-complemented strains, translated the above findings into significant outcome differences in an experimental endocarditis model. These observations indicate a significant regulation of purine biosynthesis on stringent response, and suggest the existence of a previously unknown adaptive genetic mechanism in persistent MRSA infection.<\/jats:p>","DOI":"10.1093\/infdis\/jiaa202","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T19:09:19Z","timestamp":1587496159000},"page":"1188-1198","source":"Crossref","is-referenced-by-count":25,"title":["The Stringent Response Contributes to Persistent Methicillin-Resistant Staphylococcus aureus Endovascular Infection Through the Purine Biosynthetic Pathway"],"prefix":"10.1093","volume":"222","author":[{"given":"Liang","family":"Li","sequence":"first","affiliation":[{"name":"Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold S","family":"Bayer","sequence":"additional","affiliation":[{"name":"Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, USA"},{"name":"Division of Infectious Diseases, Department of Medicine, Harbor-UCLA Medical Center, Torrance, California, USA"},{"name":"David Geffen School of Medicine at UCLA, Los Angeles, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambrose","family":"Cheung","sequence":"additional","affiliation":[{"name":"Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lou","family":"Lu","sequence":"additional","affiliation":[{"name":"Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, USA"},{"name":"Division of Infectious Diseases, Department of Medicine, Harbor-UCLA Medical Center, Torrance, California, USA"},{"name":"Division of Molecular Medicine, Department of Medicine, Harbor-UCLA Medical Center, Torrance, California, 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