<i>Staphylococcus aureus</i> biofilms release leukocidins to elicit extracellular trap formation and evade neutrophil-mediated killing

Abstract

Bacterial biofilms efficiently evade immune defenses, greatly complicating the prognosis of chronic infections. How methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) biofilms evade host immune defenses is largely unknown. This study describes some of the major mechanisms required for <i>S. aureus</i> biofilms to evade the innate immune response and provides evidence of key virulence factors required for survival and persistence of bacteria during chronic infections. Neutrophils are the most abundant white blood cells in circulation, playing crucial roles in the control and elimination of bacterial pathogens. Specifically, here we show that, unlike single-celled populations, <i>S. aureus</i> biofilms rapidly skew neutrophils toward neutrophil extracellular trap (NET) formation through the combined activity of leukocidins Panton-Valentine leukocidin and γ-hemolysin AB. By eliciting this response, <i>S. aureus</i> was able to persist, as the antimicrobial activity of released NETs was ineffective at clearing biofilm bacteria. Indeed, these studies suggest that NETs could inadvertently potentiate biofilm infections. Last, chronic infection in a porcine burn wound model clearly demonstrated that leukocidins are required for "NETosis" and facilitate bacterial survival in vivo.