Immunogenicity of Toxins during Staphylococcus aureus Infection

• Published in: Clinical infectious diseases Vol. 50; no. 1; pp. 61 - 68
• Main Authors: Verkaik, Nelianne J., Dauwalder, Olivier, Antri, Kenza, Boubekri, Ilhem, de Vogel, Corné P., Badiou, Cédric, Bes, Michèle, Vandenesch, Francçois, Tazir, Mohamed, Hooijkaas, Herbert, Verbrugh, Henri A., van Belkum, Alex, Etienne, Jerome, Lina, Gerard, Ramdani-Bouguessa, Nadjia, van Wamel, Willem J.B.
• Format: Journal Article
• Language: English
• Published: Oxford The University of Chicago Press 01.01.2010; University of Chicago Press; Oxford University Press
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies; Antibodies, Bacterial - immunology; ARTICLES AND COMMENTARIES; Bacterial diseases; Bacterial Toxins - genetics; Bacterial Toxins - immunology; Biological and medical sciences; Bones; Case-Control Studies; Child; Child, Preschool; Enterotoxins; Female; Fluorescence; Genes; Human bacterial diseases; Humans; Immune response; Immunoglobulin G - immunology; Immunoglobulins; Infant; Infant, Newborn; Infections; Infectious diseases; Leukocidins; Logistic Models; Male; Medical sciences; Middle Aged; Prevalence; Reproducibility of Results; Staphylococcal Infections - epidemiology; Staphylococcal Infections - microbiology; Staphylococcal infections, streptococcal infections, pneumococcal infections; Staphylococcus; Staphylococcus aureus; Staphylococcus aureus - genetics; Staphylococcus aureus - immunology; Staphylococcus aureus - pathogenicity; Staphylococcus infections; Statistics, Nonparametric; Toxicity; Toxins; Infection; Toxin; Immunogenicity; Bacteriosis; Bacteria; Micrococcales; Micrococcaceae; Staphylococcal infection; Staphylococcus aureus
• ISSN: 1058-4838; 1537-6591; 1537-6591
• DOI: 10.1086/648673

Background Toxins are important Staphylococcus aureus virulence factors, but little is known about their immunogenicity during infection. Here, additional insight is generated. Methods Serum samples from 206 S. aureus-infected patients and 201 hospital-admitted control subjects were analyzed for immunoglobulin (Ig) G binding to 20 toxins, using flow-cytometry based technology. Antibody levels were associated with polymerase chain reaction-defined presence of toxin genes in homologous S. aureus isolates. Results IgG levels directed to exfoliative toxin (ET) A, ETB, ghemolysin B (HlgB), leukocidin (Luk) D, LukE, LukS, staphylococcal enterotoxin (SE) A, SEE, SEH, SEI, and SElM were higher in S. aureus-infected patients than in control subjects (P <.05). Furthermore, in the S. aureus-infected patient group, IgG levels were higher if genes encoding ETA, ETB, SEA, SEC, SEH, SElQ, toxic shock syndrome toxin-1 (TSST-1), or Panton-Valentine leukocidin (PVL) were present in the infectious isolate (P < .05). Levels of anti-SEA IgG increased during infections with sea-positive (median fluorescence intensity from 11,555 to 12,388; P<.05) but not sea-negative strains. In addition, anti-LukS IgG levels increased during skin and soft-tissue infections with luk-PV-positive (median fluorescence intensity from 15,231 to 15,911; P < .05) but not luk-PV-negative strains. Bacteremia was associated with sea (odds ratio, 3.4; 95% confidence interval, 1.2–10.0) and tst (odds ratio, 5.7; 95% confidence interval, 1.6–20.8). Skin and soft-tissue infections and bone and joint infections were associated with luk-PV (odds ratio, 2.5; 95% confidence interval, 1.2–5.2). Conclusions Many toxins are expressed in vivo and recognized by the immune system during staphylococcal infections, suggesting their involvement in S. aureus pathogenesis.