Monofluorophosphate Blocks Internal Polysaccharide Synthesis in Streptococcus mutans

DEMONTE AM*; ASENCION DIEZ MD*; NALEWAY, CONRAD; IGLESIAS, AA; BALLICORA, MA

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2017

1932-6203

*Equally contributed to the workStreptococcus mutans is the leading cause of dental caries worldwide by accumulating aglycogen-like internal polysaccharide (IPS) that contributes to cariogenicitywhen sugars are in excess. Sodium monofluorophosphate (MFP) is an activeanticariogenic compound in toothpastes. Herein, we show that MFP inhibits (withan I0.5 of 1.5 mM) the S. mutans ADP-glucosepyrophosphorylase (EC 2.7.7.27), which catalyzes the key step in IPSbiosynthesis. Enzyme inhibition by MFP is similar to orthophosphate (Pi),except that the effect caused by MFP is not reverted by fructose-1,6-bisP, asoccurs with Pi. Inhibition was correlated with a decrease in acidogenesis andIPS accumulation in S. mutans cells cultured with 2 mM sodium MFP. Theseeffects were not mimicked by sodium fluoride. Considering that glycogensynthesis occurs by different pathways in mammals and bacteria, ADP-glucosepyrophosphorylase could be visualized as a molecular target for controlling S.mutans virulence. Our results strongly suggest that MFP is a suitablecompound to affect such a target, inducing an anticariogenic effect primarilyby inhibiting a key step in IPS synthesis.