Monofluorophosphate Blocks Internal Polysaccharide Synthesis in Streptococcus mutans.

Ana M. Demonte,Alberto A. Iglesias,Matias D. Asencion Diez,Miguel A. Ballicora,Conrad Naleway,Mikael Skurnik

doi:10.1371/journal.pone.0170483

Ana M. Demonte, Alberto A. Iglesias + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0170483

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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.

Highlights

It has been demonstrated that S. mutans, a resident of the normal flora of the oral cavity, is the main etiologic agent of dental caries [1,2,3]
The role of sugars on the pathogenesis of dental biofilm formation determining cariogenicity has been established in good detail [5]; and a direct relationship has been evidenced between the capacity to accumulate internal polysaccharide (IPS) and the in vivo cariogenic potential of S. mutans [6]
We report the inhibitory effect of MFP on the ADP-Glc PPase of S. mutans, which induces a reduction in IPS biosynthesis and correlates with changes in the physiological features of the microorganism

Summary

Introduction

It has been demonstrated that S. mutans, a resident of the normal flora of the oral cavity, is the main etiologic agent of dental caries [1,2,3]. Cariogenicity relies on the capacity of the bacterium to: (i) build up biofilm, (ii) acidify the extracellular milieu, and (iii) persist in an adverse environment, three uncommon feasibilities in other bacteria. These capabilities are related to the accumulation of a glycogen-like internal polysaccharide (IPS), whose attributed role is to provide a carbon source during periods of shortage with the concomitant production of acidity [4]. The role of sugars on the pathogenesis of dental biofilm formation determining cariogenicity has been established in good detail [5]; and a direct relationship has been evidenced between the capacity to accumulate IPS and the in vivo cariogenic potential of S. mutans [6].

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