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

Monofluorophosphate Blocks Internal Polysaccharide Synthesis in Streptococcus mutans

Ana M Demonte  1 , Matias D Asencion Diez  1 , Conrad Naleway  2 , Alberto A Iglesias  1 , Miguel A Ballicora  2
Affiliations

Monofluorophosphate Blocks Internal Polysaccharide Synthesis in Streptococcus mutans

Ana M Demonte et al. PLoS One. .

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.

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Conflict of interest statement

This work was supported in part by Colgate Research Funds (CN). There are no patents, products in development or marketed products to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. pH reduction from S. mutans ATCC 25175 planktonic cultures in the presence of 2 mM MFP (circles) or 1 mM NaF (triangles).
Cultures with no MFP or NaF are shown in squares.
Fig 2
Fig 2. Glycogen content from S. mutans ATCC 25175 planktonic cultures in the presence of 2 mM MFP (black bars) or 1 mM NaF (white bars).
Cultures with no MFP or NaF are shown in plaid bars.
Fig 3
Fig 3. S. mutans ADP-Glc PPase inhibition when Pi (empty circles) or MFP (filled circles) are present in the reaction mixture.
Curves were obtained from reactions conducted at 1 mM Glc-1P, 2 mM ATP and 10 mM Mg2+.
Fig 4
Fig 4. S. mutans ADP-Glc PPase inhibition curves by MFP at different concentrations (▼-1 mM, ■-3 mM, ●-5 mM and △-10mM) of ATP.
In the inset, the data represented according Dixon plots (1/v vs MFP concentration) are shown to estimate the inhibition constant.
See this image and copyright information in PMC

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