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

ABSTRACT:

Background

?Development of methicillin-resistant Staphylococcus aureus (MRSA) pneumonia after a respiratory viral infection is frequently fatal in children. In mice, S. aureus ?-toxin directly injures pneumocytes and increases mortality, whereas ?-toxin blockade mitigates disease. The role of ?-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-?-toxin antibody titers and functional ?-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 ?-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 ?-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-?-toxin titer and functional neutralization capacity. MRSA ?-toxin production from patient isolates correlated with initial serologic titers and with mortality in murine pneumonia.

Conclusions

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

SUBMITTER: Yu KO 

PROVIDER: S-EPMC5144732 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature