Recombinant human DNase I decreases biofilm and increases antimicrobial susceptibility in staphylococci

Extracellular DNA is an adhesive component of staphylococcal biofilms. The aim of this study was to evaluate the antibiofilm activity of recombinant human DNase I (rhDNase) against Staphylococcus aureus and Staphylococcus epidermidis. Using a 96-well microtiter plate crystal-violet binding assay, we found that biofilm formation by S. aureus was efficiently inhibited by rhDNase at 1-4 microg l⁻¹, and preformed S. aureus biofilms were efficiently detached in 2 min by rhDNase at 1 mg l⁻¹. Pretreatment of S. aureus biofilms for 10 min with 10 mg l⁻¹ rhDNase increased their sensitivity to biocide killing by 4-5 log units. rhDNase at 10 mg l⁻¹ significantly inhibited biofilm formation by S. epidermidis in medium supplemented with sub-MICs of antibiotics. We also found that rhDNase significantly increased the survival of S. aureus-infected Caenorhabditis elegans nematodes treated with tobramycin compared with nematodes treated with tobramycin alone. We concluded that rhDNase exhibits potent antibiofilm and antimicrobial-sensitizing activities against S. aureus and S. epidermidis at clinically achievable concentrations. rhDNase, either alone or in combination with antimicrobial agents, may have applications in treating or preventing staphylococcal biofilm-related infections.