Staphylococcus aureus α-Toxin Response Distinguishes Respiratory Virus-Methicillin-Resistant S. aureus Coinfection in Children

J Infect Dis. 2016 Dec 1;214(11):1638-1646. doi: 10.1093/infdis/jiw441. Epub 2016 Sep 20.


Background: Development of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia after a respiratory viral infection is frequently fatal in children. In mice, S. aureus α-toxin directly injures pneumocytes and increases mortality, whereas α-toxin blockade mitigates disease. The role of α-toxin in pediatric staphylococcal-viral coinfection is unclear.

Methods: We enrolled children across 34 North American pediatric intensive care units with acute respiratory failure and suspected influenza virus infection. Serial serum anti-α-toxin antibody titers and functional α-toxin neutralization capacity were compared across children coinfected with MRSA or methicillin-susceptible S. aureus (MSSA) and control children infected with influenza virus only. MRSA isolates were tested for α-toxin production and lethality in a murine pneumonia model.

Results: Influenza virus was identified in 22 of 25 children with MRSA coinfection (9 died) and 22 patients with MSSA coinfection (all survived). Initial α-toxin-specific antibody titers were similar, compared with those in the 13 controls. In patients with serial samples, only MRSA-coinfected patients showed time-dependent increases in anti-α-toxin titer and functional neutralization capacity. MRSA α-toxin production from patient isolates correlated with initial serologic titers and with mortality in murine pneumonia.

Conclusions: These data implicate α-toxin as a relevant antigen in severe pediatric MRSA pneumonia associated with respiratory viral infection, supporting a potential role for toxin-neutralizing therapy.

Keywords: bacteria; influenza; intensive care unit; pediatric; pneumonia; respiratory failure.

MeSH terms

  • Adolescent
  • Animal Experimentation
  • Animals
  • Antibodies, Bacterial / blood*
  • Bacterial Toxins / immunology*
  • Bacterial Toxins / toxicity*
  • Child
  • Child, Preschool
  • Coinfection / complications
  • Coinfection / pathology*
  • Female
  • Hemolysin Proteins / immunology*
  • Hemolysin Proteins / toxicity*
  • Humans
  • Influenza, Human / complications*
  • Intensive Care Units
  • Male
  • Methicillin Resistance
  • Mice
  • Neutralization Tests
  • North America
  • Respiratory Insufficiency / pathology*
  • Staphylococcal Infections / complications
  • Staphylococcal Infections / pathology*
  • Staphylococcus aureus / classification
  • Staphylococcus aureus / isolation & purification
  • Survival Analysis


  • Antibodies, Bacterial
  • Bacterial Toxins
  • Hemolysin Proteins
  • staphylococcal alpha-toxin