Leukocidins and the Nuclease Nuc Prevent Neutrophil-Mediated Killing of Staphylococcus aureus Biofilms

Abstract

Bacterial biofilms are linked with chronic infections and have properties distinct from those of planktonic, single-celled bacteria. The virulence mechanisms associated with <i>Staphylococcus aureus</i> biofilms are becoming better understood. Human neutrophils are critical for the innate immune response to <i>S. aureus</i> infection. Here, we describe two virulence strategies that converge to promote the ability of <i>S. aureus</i> biofilms to evade killing by neutrophils. Specifically, we show that while neutrophils exposed to <i>S. aureus</i> biofilms produce extracellular traps (NETs) and phagocytose bacteria, both mechanisms are inefficient in clearance of the biofilm biomass. This is attributed to the leukocidin LukAB, which promotes <i>S. aureus</i> survival during phagocytosis. We also show that the persistence of biofilm bacteria trapped in NETs is facilitated by <i>S. aureus</i> nuclease (Nuc)-mediated degradation of NET DNA. This study describes key aspects of the interaction between primary human neutrophils and <i>S. aureus</i> biofilms and provides insight into how <i>S. aureus</i> evades the neutrophil response to cause persistent infections.