ArticleJournal of clinical microbiology2015
Characterization of alpha-toxin hla gene variants, alpha-toxin expression levels, and levels of antibody to alpha-toxin in hemodialysis and postsurgical patients with Staphylococcus aureus bacteremia.
Article in Journal of clinical microbiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- Safety, Tolerability, and Pharmacokinetics of MEDI4893, an Investigational, Extended-Half-Life, Anti-Staphylococcus aureus Alpha-Toxin Human Monoclonal Antibody, in Healthy Adults.Antimicrobial agents and chemotherapy · 2017Trial
- Human anti-alpha-hemolysin scFvs mitigate toxin-mediated damage in a mouse model of MRSA pneumonia.Applied microbiology and biotechnology · 2026Article
- The lack of a biorepository during vaccine trials: A lost opportunity to understand staphylococcal immunity.Vaccine · 2025Article
- Repurposing Diflunisal as an Antivirulence Agent AgainstInfectious microbes & diseases · 2025Article
- Integrated immunodominant epitope discovery for dual-purpose rapid and economical diagnostic and immunoprotective applications against MRSA.Frontiers in immunology · 2025Article
- Article
- Anti-Alpha-Toxin Antibody Responses and Clinical Outcomes ofJournal of Korean medical science · 2023Article
- Article
- Correlations of Host and Bacterial Characteristics with Clinical Parameters and Survival inJournal of clinical medicine · 2021Article
- Immunodominance of Epitopes and Protective Efficacy of HI Antigen Are Differentially Altered Using Different Adjuvants in a Mouse Model ofFrontiers in immunology · 2021Article
- Toxin-Triggered Interleukin-1 Receptor Signaling Enables Early-Life Discrimination of Pathogenic versus Commensal Skin Bacteria.Cell host & microbe · 2019Article
- Article
- Associations of pathogen-specific and host-specific characteristics with disease outcome in patients withClinical & translational immunology · 2019Article
- Alanine Scanning Mutagenesis of the MEDI4893 (Suvratoxumab) Epitope Reduces Alpha Toxin Lytic ActivityAntimicrobial agents and chemotherapy · 2018Article
- Virulence gene profiles: alpha-hemolysin and clonal diversity in Staphylococcus aureus isolates from bovine clinical mastitis in China.BMC veterinary research · 2018Article
- Prevalence of IgG and Neutralizing Antibodies against Staphylococcus aureus Alpha-Toxin in Healthy Human Subjects and Diverse Patient Populations.Infection and immunity · 2018Article
- The antibody response in the bovine mammary gland is influenced by the adjuvant and the site of subcutaneous vaccination.Veterinary research · 2018Article
- S. aureus Evades Macrophage Killing through NLRP3-Dependent Effects on Mitochondrial Trafficking.Cell reports · 2018Article
- Characterisation of anti-alpha toxin antibody levels and colonisation status after administration of an investigational human monoclonal antibody, MEDI4893, againstClinical & translational immunology · 2018Article
- Molecular Epidemiology ofFrontiers in microbiology · 2018Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
Alpha-toxin is a major Staphylococcus aureus virulence factor. This study evaluated potential relationships between in vitro alpha-toxin expression of S. aureus bloodstream isolates, anti-alpha-toxin antibody in serum of patients with S. aureus bacteremia (SAB), and clinical outcomes in 100 hemodialysis and 100 postsurgical SAB patients. Isolates underwent spa typing and hla 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 hla (197/200; 98.5%) and expressed alpha-toxin (173/200; 86.5%). In vitro alpha-toxin levels were inversely associated with survival (cure, 2.19 μg/ml, versus failure, 1.09 μg/ml; P < 0.01). Both neutralizing (hemodialysis, 1.26 IU/ml, versus postsurgical, 0.95; P < 0.05) and IgG (hemodialysis, 1.94 IU/ml, versus postsurgical, 1.27; P < 0.05) antibody levels were higher in the hemodialysis population. Antibody levels were also significantly higher in patients infected with alpha-toxin-expressing S. aureus isolates (P < 0.05). Levels of both neutralizing antibodies and IgG were similar among patients who were cured and those not cured (failures). Sequence analysis of hla revealed 12 distinct hla 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 S. aureus isolates. Higher in vitro alpha-toxin levels were associated with a positive clinical outcome. Although patients infected with alpha-toxin-producing S. aureus exhibited higher anti-alpha-toxin antibody levels, these levels were not associated with a better clinical outcome in this study.
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