title: A novel compound to maintain a healthy oral plaque ecology in vitro.
abstract: OBJECTIVE
  Dental caries is caused by prolonged episodes of low pH due to acid production by oral biofilms. Bacteria within such biofilms communicate via quorum sensing (QS). QS regulates several phenotypic biofilm parameters, such as biofilm formation and the production of virulence factors. In this study, we evaluated the effect of several QS modifiers on growth and the cariogenic potential of microcosm oral biofilms.
  
  
  METHODS
  Biofilms were inoculated with pooled saliva and cultured in the presence of sucrose for 48 and 96 h. QS modifiers (or carrier controls) were continuously present. Lactic acid accumulation capacities were compared to evaluate the cariogenic potential of the biofilms. Subsequently, biofilm growth was quantified by determining colony forming unit counts (CFUs) and their ecology by 16S rDNA-based microbiome analyses. The minimal inhibitory concentration (MIC) for several Streptococcus spp. was determined using microbroth dilution.
  
  
  RESULTS
  Of the tested QS modifiers only 3-oxo-N-(2-oxocyclohexyl)dodecanamide (3-Oxo-N) completely abolished lactic acid accumulation by the biofilms without affecting biofilm growth. This compound was selected for further investigation. The active range of 3-Oxo-N was 10-100 µM. The homologous QS molecule, acyl homoserine lactone C12, did not counteract the reduction in lactic acid accumulation, suggesting a mechanism other than QS inhibition. Microbial ecology analyses showed a reduction in the relative abundance of Streptococcus spp. in favor of the relative abundance of Veillonella spp. in the 3-Oxo-N exposed biofilms. The MIC of 3-Oxo-N for several streptococcal species varied between 8 and 32 µM.
  
  
  CONCLUSIONS
  3-Oxo-N changes the ecological homeostasis of in vitro dental plaque. It reduces its cariogenic potential by minimizing lactic acid accumulation. Based on our in vitro data, 3-Oxo-N represents a promising compound in maintaining a healthy, non-cariogenic, ecology in in vivo dental plaque.
authors.affiliation: Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University, Amsterdam, The Netherlands.|Top Institute Food and Nutrition, Wageningen, The Netherlands.
authors.forename: Marleen M
authors.initials: MM
authors.lastname: Janus
authors.affiliation: Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University, Amsterdam, The Netherlands.|Top Institute Food and Nutrition, Wageningen, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Crielaard
authors.affiliation: Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University, Amsterdam, The Netherlands.|Top Institute Food and Nutrition, Wageningen, The Netherlands.
authors.forename: Egija
authors.initials: E
authors.lastname: Zaura
authors.affiliation: Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University, Amsterdam, The Netherlands.|Top Institute Food and Nutrition, Wageningen, The Netherlands.|Microbiology and Systems Biology, TNO Earth, Environmental and Life Sciences, Zeist, The Netherlands.
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Keijser
authors.affiliation: Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University, Amsterdam, The Netherlands.|Top Institute Food and Nutrition, Wageningen, The Netherlands.
authors.forename: Bernd W
authors.initials: BW
authors.lastname: Brandt
authors.affiliation: Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University, Amsterdam, The Netherlands.|Top Institute Food and Nutrition, Wageningen, The Netherlands; b.krom@acta.nl.
authors.forename: Bastiaan P
authors.initials: BP
authors.lastname: Krom
keywords: 3-oxo-N-(2-oxocyclohexyl)dodecanamide; In vitro biofilms; caries; dental plaque; healthy ecology; quorum sensing