Antibiofilm Activities of a Novel Chimeolysin against Streptococcus mutans under Physiological and Cariogenic Conditions

Antimicrob Agents Chemother. 2016 Nov 21;60(12):7436-7443. doi: 10.1128/AAC.01872-16. Print 2016 Dec.

Abstract

Streptococcus mutans often survives as a biofilm on the tooth surface and contributes to the development of dental caries. We investigated the efficacy of ClyR, an engineered chimeolysin, against S. mutans biofilms under physiological and cariogenic conditions. Susceptibility tests showed that ClyR was active against all clinical S. mutans isolates tested as well as S. mutans biofilms that displayed resistance to penicillin. The S. mutans biofilms that formed on hydroxyapatite discs under physiological sugar conditions and cariogenic conditions were reduced ∼2 logs and 3 logs after treatment with 100 μg/ml ClyR, respectively. In comparison, only a 1-log reduction was observed in the chlorhexidine gluconate (ChX)-treated group, and no killing effect was observed in the NaF-treated group. A mouse dental colonization model showed that repeated use of ClyR for 3 weeks (5 μg/day) reduced the number of colonized S. mutans cells in the dental plaques significantly (P < 0.05) and had no harmful effects on the mice. Furthermore, toxicity was not noted at concentrations exceeding those used for the in vitro and in vivo studies, and ClyR-specific antibodies could not be detected in mouse saliva after repeated use of ClyR in the oral cavity. Our data collectively demonstrate that ClyR is active against S. mutans biofilms both in vitro and in vivo, thus representing a preventative or therapeutic agent for use against dental caries.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / biosynthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacteriophages / chemistry
  • Bacteriophages / enzymology
  • Biofilms / drug effects*
  • Biofilms / growth & development
  • CHO Cells
  • Caco-2 Cells
  • Cell Survival / drug effects
  • Chlorhexidine / analogs & derivatives
  • Chlorhexidine / pharmacology
  • Cricetulus
  • Dental Caries / drug therapy*
  • Dental Caries / microbiology
  • Dental Plaque / drug therapy*
  • Dental Plaque / microbiology
  • Disease Models, Animal
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Female
  • Gene Expression
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • N-Acetylmuramoyl-L-alanine Amidase / biosynthesis
  • N-Acetylmuramoyl-L-alanine Amidase / genetics
  • N-Acetylmuramoyl-L-alanine Amidase / pharmacology*
  • Penicillins / pharmacology
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / genetics
  • Recombinant Proteins / pharmacology
  • Saliva / chemistry
  • Sodium Fluoride / pharmacology
  • Streptococcus mutans / drug effects*
  • Streptococcus mutans / growth & development
  • Viral Proteins / biosynthesis
  • Viral Proteins / genetics
  • Viral Proteins / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Penicillins
  • Recombinant Proteins
  • Viral Proteins
  • Sodium Fluoride
  • N-Acetylmuramoyl-L-alanine Amidase
  • chlorhexidine gluconate
  • Chlorhexidine