Staphylococcus aureus induces neutrophil extracellular traps (NETs) and neutralizes their bactericidal potential

Neutrophil extracellular traps (NETs) are considered part of the innate human immune system because they are involved in host defense during bacterial infections. NETs are formed by activated neutrophils and consist of a DNA backbone combined with proteins with different biological functions. The activity of NETs can be significantly reduced by a Staphylococcus aureus DNase, which degrades the DNA backbone and enables the liberation of bacteria from NETs, and by Eap, a secreted protein which binds and aggregates linearized DNA, suppressing the formation of NETs. Furthermore, the pathogen can resist NET-mediated killing by expressing the surface protein FnBPB, which neutralizes the bactericidal activity of histones. Finally, the anti-staphylococcal activity of NETs is counteracted and blocked by S. aureus biofilm. Staphylococcal cells and several virulence factors such as protein A and phenol-soluble modulins can also elicit the formation of NETs which in turn can cause tissue injury, enhancing bacterial performance in host colonization. The identification of additional virulence factors involved in NET formation/neutralization could provide the basis for therapeutic interventions against this formidable pathogen.