title: Treatment of Oral Biofilms by a D-Enantiomeric Peptide.
abstract: Almost all dental diseases are caused by biofilms that consist of multispecies communities. DJK-5, which is a short D-enantiomeric, protease-resistant peptide with broad-spectrum anti-biofilm activity, was tested for its effect on oral multispecies biofilms. Peptide DJK-5 at 10 μg/mL effectively prevented the growth of these microbes in culture media in a time-dependent manner. In addition to the prevention of growth, peptide DJK-5 completely killed both Streptococcus mutans and Enterococcus faecalis suspended from biofilms after 30 minutes of incubation in liquid culture media. DJK-5 also led to the effective killing of microbes in plaque biofilm. The proportion of bacterial cells killed by 10 μg/mL of DJK-5 was similar after 1 and 3 days, both exceeding 85%. DJK-5 was able to significantly prevent biofilm formation over 3 days (P = 0.000). After 72 hours of exposure, DJK-5 significantly reduced and almost completely prevented plaque biofilm production by more than 90% of biovolume compared to untreated controls (P = 0.000). The proportion of dead biofilm bacteria at the 10 μg/mL DJK-5 concentration was similar for 1- and 3-day-old biofilms, whereby >86% of the bacteria were killed. DJK-5 was also able to kill >79% and >85% of bacteria, respectively, after one-time and three brief treatments of 3-day-old biofilms. The combination of DJK-5 and chlorhexidine showed the best bacterial killing among all treatments, with ~83% and >88% of bacterial cells killed after 1 and 3 minutes, respectively. No significant difference was found in the percentage of biofilm killing amongst three donor plaque samples after DJK-5 treatment. In particular, DJK-5 showed strong performance in inhibiting biofilm development and eradicating pre-formed oral biofilms compared to L-enantiomeric peptide 1018. DJK-5 was very effective against oral biofilms when used alone or combined with chlorhexidine, and may be a promising agent for use in oral anti-biofilm strategies in the future.
authors.affiliation: Division of Endodontics, Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Tian
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Division of Endodontics, Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Zhejun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
authors.affiliation: Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.|Synthetic Biology Group, MIT Synthetic Biology Center, Research Laboratory of Electronics, Department of Biological Engineering, Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Broad Institute of MIT and Harvard University, Cambridge, Massachusetts, United States of America.
authors.forename: César
authors.initials: C
authors.lastname: de la Fuente-Núñez
authors.affiliation: Division of Endodontics, Department of Oral Biological and Medical Sciences, Faculty of Dentistry, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Markus
authors.initials: M
authors.lastname: Haapasalo
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D013293:Enterococcus faecalis / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D009055:Mouth / Q000382:microbiology*; D009842:Oligopeptides / Q000494:pharmacology*; D013295:Streptococcus mutans / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; C000602801:DJK-5 peptide; D009842:Oligopeptides