title: Recombinant human DNase I decreases biofilm and increases antimicrobial susceptibility in staphylococci.
abstract: 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 μg 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.
authors.affiliation: Department of Oral Biology, New Jersey Dental School, Newark, NJ 07103, USA. kaplanjb@umdnj.edu
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kaplan
authors.forename: Karen
authors.initials: K
authors.lastname: LoVetri
authors.forename: Silvia T
authors.initials: ST
authors.lastname: Cardona
authors.forename: Srinivasa
authors.initials: S
authors.lastname: Madhyastha
authors.forename: Irina
authors.initials: I
authors.lastname: Sadovskaya
authors.forename: Saïd
authors.initials: S
authors.lastname: Jabbouri
authors.forename: Era A
authors.initials: EA
authors.lastname: Izano
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000382:microbiology; D003850:Deoxyribonuclease I / Q000235:genetics / Q000494:pharmacology*; D029968:Escherichia coli Proteins / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests; D011995:Recombination, Genetic; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000254:growth & development; D014031:Tobramycin / Q000494:pharmacology
chemical_list: C479827:AAP protein, E coli; D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D003850:Deoxyribonuclease I; D014031:Tobramycin