Monofluorophosphate Blocks Internal Polysaccharide Synthesis in Streptococcus mutans

PLoS One. 2017 Jan 26;12(1):e0170483. doi: 10.1371/journal.pone.0170483. eCollection 2017.

Abstract

Streptococcus mutans is the leading cause of dental caries worldwide by accumulating a glycogen-like internal polysaccharide (IPS) that contributes to cariogenicity when sugars are in excess. Sodium monofluorophosphate (MFP) is an active anticariogenic compound in toothpastes. Herein, we show that MFP inhibits (with an I0.5 of 1.5 mM) the S. mutans ADP-glucose pyrophosphorylase (EC 2.7.7.27), which catalyzes the key step in IPS biosynthesis. Enzyme inhibition by MFP is similar to orthophosphate (Pi), except that the effect caused by MFP is not reverted by fructose-1,6-bisP, as occurs with Pi. Inhibition was correlated with a decrease in acidogenesis and IPS accumulation in S. mutans cells cultured with 2 mM sodium MFP. These effects were not mimicked by sodium fluoride. Considering that glycogen synthesis occurs by different pathways in mammals and bacteria, ADP-glucose pyrophosphorylase could be visualized as a molecular target for controlling S. mutans virulence. Our results strongly suggest that MFP is a suitable compound to affect such a target, inducing an anticariogenic effect primarily by inhibiting a key step in IPS synthesis.

MeSH terms

  • Dental Caries / microbiology*
  • Dental Caries / prevention & control
  • Fluorides / pharmacology*
  • Phosphates / pharmacology*
  • Polysaccharides, Bacterial / biosynthesis*
  • Sodium Fluoride / pharmacology
  • Streptococcus mutans / drug effects*
  • Streptococcus mutans / metabolism
  • Toothpastes / pharmacology*

Substances

  • Phosphates
  • Polysaccharides, Bacterial
  • Toothpastes
  • fluorophosphate
  • Sodium Fluoride
  • Fluorides

Grants and funding

This work was supported by Colgate Research Funds (CN) and by grants to AAI from UNL [CAI+D], ANPCyT [PICT’14 3256] and to MDAD [PICT’14 3362] and to MAB from the National Science Foundation [MCB 1024945]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. MDAD and AAI are members of the Research Career from CONICET. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.