Staphylococcus aureus biofilm extracellular DNA neutralizes the antimicrobial activity of histone H3

Staphylococcus aureus is an opportunistic pathogen that forms robust biofilms. This poses several challenges to the host in successfully clearing the pathogen, thus leading to chronic infections. S. aureus biofilms combat neutrophils by releasing pore-forming toxins called leukocidins. This leads to the induction of neutrophil extracellular traps (NETs) and neutrophil death. NETs are primarily composed of host DNA laced with several potent antimicrobials, including histones. While NETs entrap microbes, the nuclease produced by S. aureus degrades NETs, potentially releasing NET-associated antimicrobials. It is still unknown how S. aureus can persist in a chronic infection despite the presence of several NET-associated antimicrobials. Our studies revealed that histone H3 is sequestered by S. aureus-derived extracellular DNA (eDNA) of the biofilm matrix. This resulted in the architectural modification of the biofilm due to the formation of eDNA-H3 aggregates and protection of S. aureus within the biofilm from the potential bactericidal effects of H3.