{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:43:59Z","timestamp":1791218639006,"version":"4.1.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2002,5,1]],"date-time":"2002-05-01T00:00:00Z","timestamp":1020211200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2002,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The majority of infections with glycopeptide intermediate-level resistant\n            <jats:italic>Staphylococcus aureus<\/jats:italic>\n            (GISA) originate in biomedical devices, suggesting a possible increased ability of these strains to produce biofilm. Loss of function of the accessory gene regulator (\n            <jats:italic>agr<\/jats:italic>\n            ) of\n            <jats:italic>S. aureus<\/jats:italic>\n            has been suggested to confer an enhanced ability to bind to polystyrene. We studied\n            <jats:italic>agr<\/jats:italic>\n            in GISA, hetero-GISA, and related glycopeptide-susceptible\n            <jats:italic>S. aureus<\/jats:italic>\n            isolates. All GISA strains from diverse geographic origins belong to\n            <jats:italic>agr<\/jats:italic>\n            group II. All GISA strains were defective in\n            <jats:italic>agr<\/jats:italic>\n            function, as demonstrated by their inability to produce delta-hemolysin. Hetero-GISA isolate A5940 demonstrated a nonsense mutation in\n            <jats:italic>agrA<\/jats:italic>\n            that was not present in a pulsed-field gel electrophoresis-indistinguishable vancomycin-susceptible isolate from the same patient. Various other\n            <jats:italic>agr<\/jats:italic>\n            point mutations were noted in several clinical GISA and hetero-GISA isolates. A laboratory-generated\n            <jats:italic>agr<\/jats:italic>\n            -null strain demonstrated a small but reproducible increase in vancomycin heteroresistance after growth in vitro in subinhibitory concentrations of vancomycin. This was not seen in the isogenic\n            <jats:italic>agr<\/jats:italic>\n            group II parent strain in which\n            <jats:italic>agr<\/jats:italic>\n            was intact. The in vitro bactericidal activity of vancomycin was attenuated in the\n            <jats:italic>agr<\/jats:italic>\n            -null strain compared to the parent strain. These findings imply that compromised\n            <jats:italic>agr<\/jats:italic>\n            function is advantageous to clinical isolates of\n            <jats:italic>S. aureus<\/jats:italic>\n            toward the development of vancomycin heteroresistance, perhaps through the development of vancomycin tolerance.\n          <\/jats:p>","DOI":"10.1128\/aac.46.5.1492-1502.2002","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:09:01Z","timestamp":1027764541000},"page":"1492-1502","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":323,"title":["Accessory Gene Regulator (\n            <i>agr<\/i>\n            ) Locus in Geographically Diverse\n            <i>Staphylococcus aureus<\/i>\n            Isolates with Reduced Susceptibility to Vancomycin"],"prefix":"10.1128","volume":"46","author":[{"given":"George","family":"Sakoulas","sequence":"first","affiliation":[{"name":"Department of Medicine"},{"name":"Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George M.","family":"Eliopoulos","sequence":"additional","affiliation":[{"name":"Department of Medicine"},{"name":"Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Robert C.","family":"Moellering","sequence":"additional","affiliation":[{"name":"Department of Medicine"},{"name":"Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Wennersten","sequence":"additional","affiliation":[{"name":"Department of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lata","family":"Venkataraman","sequence":"additional","affiliation":[{"name":"Division of Laboratory and Transfusion Medicine, Department of Pathology, Beth Israel Deaconess Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard P.","family":"Novick","sequence":"additional","affiliation":[{"name":"Skirball Institute of Biomolecular Medicine and New York University School of Medicine, New York, New York 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard S.","family":"Gold","sequence":"additional","affiliation":[{"name":"Department of Medicine"},{"name":"Harvard Medical School, Boston, Massachusetts 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.17.3389"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.6.1714-1720.2001"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.183.17.5171-5179.2001"},{"key":"e_1_3_2_6_2","first-page":"1165","volume":"48","year":"2000","unstructured":"Centers for Disease Control and Prevention. 2000. 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