{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T12:01:30Z","timestamp":1783512090814,"version":"3.55.0"},"reference-count":62,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"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":["J Clin Microbiol"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Alpha-toxin is a major\n            <jats:named-content content-type=\"genus-species\">Staphylococcus aureus<\/jats:named-content>\n            virulence factor. This study evaluated potential relationships between\n            <jats:italic>in vitro<\/jats:italic>\n            alpha-toxin expression of\n            <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n            bloodstream isolates, anti-alpha-toxin antibody in serum of patients with\n            <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n            bacteremia (SAB), and clinical outcomes in 100 hemodialysis and 100 postsurgical SAB patients. Isolates underwent\n            <jats:italic>spa<\/jats:italic>\n            typing and\n            <jats:italic>hla<\/jats:italic>\n            sequencing. Serum anti-alpha-toxin IgG and neutralizing antibody levels were measured by using an enzyme-linked immunosorbent assay and a red blood cell (RBC)-based hemolysis neutralization assay. Neutralization of alpha-toxin by an anti-alpha-toxin monoclonal antibody (MAb MEDI4893) was tested in an RBC-based lysis assay. Most isolates encoded\n            <jats:italic>hla<\/jats:italic>\n            (197\/200; 98.5%) and expressed alpha-toxin (173\/200; 86.5%).\n            <jats:italic>In vitro<\/jats:italic>\n            alpha-toxin levels were inversely associated with survival (cure, 2.19 \u03bcg\/ml, versus failure, 1.09 \u03bcg\/ml;\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.01). Both neutralizing (hemodialysis, 1.26 IU\/ml, versus postsurgical, 0.95;\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05) and IgG (hemodialysis, 1.94 IU\/ml, versus postsurgical, 1.27;\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05) antibody levels were higher in the hemodialysis population. Antibody levels were also significantly higher in patients infected with alpha-toxin-expressing\n            <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n            isolates (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05). Levels of both neutralizing antibodies and IgG were similar among patients who were cured and those not cured (failures). Sequence analysis of\n            <jats:italic>hla<\/jats:italic>\n            revealed 12 distinct\n            <jats:italic>hla<\/jats:italic>\n            genotypes, and all genotypic variants were susceptible to a neutralizing monoclonal antibody in clinical development (MEDI4893). These data demonstrate that alpha-toxin is highly conserved in clinical\n            <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n            isolates. Higher\n            <jats:italic>in vitro<\/jats:italic>\n            alpha-toxin levels were associated with a positive clinical outcome. Although patients infected with alpha-toxin-producing\n            <jats:named-content content-type=\"genus-species\">S. aureus<\/jats:named-content>\n            exhibited higher anti-alpha-toxin antibody levels, these levels were not associated with a better clinical outcome in this study.\n          <\/jats:p>","DOI":"10.1128\/jcm.02023-14","type":"journal-article","created":{"date-parts":[[2014,11,13]],"date-time":"2014-11-13T07:26:38Z","timestamp":1415863598000},"page":"227-236","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":50,"title":["Characterization of Alpha-Toxin\n            <i>hla<\/i>\n            Gene Variants, Alpha-Toxin Expression Levels, and Levels of Antibody to Alpha-Toxin in Hemodialysis and Postsurgical Patients with Staphylococcus aureus Bacteremia"],"prefix":"10.1128","volume":"53","author":[{"given":"Batu K.","family":"Sharma-Kuinkel","sequence":"first","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuling","family":"Wu","sequence":"additional","affiliation":[{"name":"MedImmune, LLC, Gaithersburg, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Tabor","sequence":"additional","affiliation":[{"name":"MedImmune, LLC, Gaithersburg, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoyin","family":"Mok","sequence":"additional","affiliation":[{"name":"MedImmune, LLC, Gaithersburg, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bret R.","family":"Sellman","sequence":"additional","affiliation":[{"name":"MedImmune, LLC, Gaithersburg, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Jenkins","sequence":"additional","affiliation":[{"name":"MedImmune, LLC, Gaithersburg, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yu","sequence":"additional","affiliation":[{"name":"MedImmune, LLC, Gaithersburg, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hasan S.","family":"Jafri","sequence":"additional","affiliation":[{"name":"MedImmune, LLC, Gaithersburg, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H.","family":"Rude","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicia","family":"Ruffin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiley A.","family":"Schell","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence P.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua T.","family":"Thaden","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia A.","family":"Messina","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Vance G.","family":"Fowler","sequence":"additional","affiliation":[{"name":"Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA"},{"name":"Duke Clinical Research Institute, Durham, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark T.","family":"Esser","sequence":"additional","affiliation":[{"name":"MedImmune, LLC, Gaithersburg, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"e394","article-title":"Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association. 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