title: Antibiofilm Activities of a Novel Chimeolysin against Streptococcus mutans under Physiological and Cariogenic Conditions.
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.
authors.affiliation: Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Yang
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Bi
authors.affiliation: Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland, USA.
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Shang
authors.affiliation: Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Mengyue
authors.initials: M
authors.lastname: Wang
authors.affiliation: Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland, USA.
authors.forename: Sara B
authors.initials: SB
authors.lastname: Linden
authors.affiliation: Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China 1004809372@whu.edu.cn nelsond@umd.edu hpwei@wh.iov.cn.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland, USA 1004809372@whu.edu.cn nelsond@umd.edu hpwei@wh.iov.cn.|Department of Veterinary Medicine, University of Maryland, College Park, Maryland, USA.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Nelson
authors.affiliation: Key Laboratory of Special Pathogens and Biosafety, Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China 1004809372@whu.edu.cn nelsond@umd.edu hpwei@wh.iov.cn.
authors.forename: Hongping
authors.initials: H
authors.lastname: Wei
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology*; D001435:Bacteriophages / Q000737:chemistry / Q000201:enzymology; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D016466:CHO Cells; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D002710:Chlorhexidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003412:Cricetulus; D003731:Dental Caries / Q000188:drug therapy* / Q000382:microbiology; D003773:Dental Plaque / Q000188:drug therapy* / Q000382:microbiology; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D010406:Penicillins / Q000494:pharmacology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D012463:Saliva / Q000737:chemistry; D012969:Sodium Fluoride / Q000494:pharmacology; D013295:Streptococcus mutans / Q000187:drug effects* / Q000254:growth & development; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D010406:Penicillins; D011994:Recombinant Proteins; D014764:Viral Proteins; D012969:Sodium Fluoride; D009238:N-Acetylmuramoyl-L-alanine Amidase; C010882:chlorhexidine gluconate; D002710:Chlorhexidine