title: Mechanistic, genomic and proteomic study on the effects of BisGMA-derived biodegradation product on cariogenic bacteria.
abstract: Investigate the effects of a Bis-phenyl-glycidyl-dimethacrylate (BisGMA) biodegradation product, bishydroxypropoxyphenyl-propane (BisHPPP), on gene expression and protein synthesis of cariogenic bacteria.
  
  
  
  Quantitative real-time polymerase chain reaction was used to investigate the effects of BisHPPP on the expression of specific virulence-associated genes, i.e. gtfB, gtfC, gbpB, comC, comD, comE and atpH in Streptococcus mutans UA159. Possible mechanisms for bacterial response to BisHPPP were explored using gene knock-out and associated complemented strains of the signal peptide encoding gene, comC. The effects of BisHPPP on global gene and protein expression was analyzed using microarray and quantitative proteomics. The role of BisHPPP in glucosyltransferase (GTF) enzyme activity of S. mutans biofilms was also measured.
  
  
  
  BisHPPP (0.01, 0.1mM) up-regulated gtfB/C, gbpB, comCDE, and atpH most pronounced in biofilms at cariogenic pH (5.5). The effects of BisHPPP on the constructed knock-out and complemented strains of comC from quorum-sensing system, implicated this signaling pathway in up-regulation of the virulence-associated genes. Microarray and proteomics identified BisHPPP-regulated genes and proteins involved in biofilm formation, carbohydrate transport, acid tolerance and stress-response. GTF activity was higher in BisHPPP-exposed biofilms when compared to no-BisHPPP conditions.
  
  
  
  These findings provide insight into the genetic and physiological pathways and mechanisms that help explain S. mutans adaptation to restorative conditions that are conducive to increased secondary caries around resin composite restorations and may provide guidance to clinicians' decision on the selection of dental materials when considering the long term oral health of patients and the interactions of composite resins with oral bacteria.
authors.affiliation: Dental Research Institute, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Lida
authors.initials: L
authors.lastname: Sadeghinejad
authors.affiliation: Dental Research Institute, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Dennis G
authors.initials: DG
authors.lastname: Cvitkovitch
authors.affiliation: Schulich Dentistry and Department of Biochemistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: Walter L
authors.initials: WL
authors.lastname: Siqueira
authors.affiliation: Department of Restorative Dentistry, School of Dentistry, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Merritt
authors.affiliation: Dental Research Institute, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
authors.forename: J Paul
authors.initials: JP
authors.lastname: Santerre
authors.affiliation: Dental Research Institute, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada. Electronic address: yoav.finer@dentistry.utoronto.ca.
authors.forename: Yoav
authors.initials: Y
authors.lastname: Finer
mesh_terms: D001426:Bacterial Proteins; D018441:Biofilms; D017438:Bisphenol A-Glycidyl Methacrylate / Q000378:metabolism / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D040901:Proteomics; D013295:Streptococcus mutans / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D017438:Bisphenol A-Glycidyl Methacrylate
keywords: Biodegradation; Biofilm; Dental adhesive; Gene expression; Microarray; Proteomics; Resin composite; Secondary caries; Streptococcus mutans