Demonte Ana M, Asencion Diez Matias D, Naleway Conrad, Iglesias Alberto A, Ballicora Miguel A
Laboratorio de Enzimología Molecular, Instituto de Agrobiotecnología del Litoral (UNL-CONICET), Santa Fe, Argentina.
Department of Chemistry and Biochemistry, Loyola University Chicago, Chicago, Illinois, United States of America.
PLoS One. 2017 Jan 26;12(1):e0170483. doi: 10.1371/journal.pone.0170483. eCollection 2017.
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.
变形链球菌是全球龋齿的主要病因，它通过积累一种糖原样胞内多糖（IPS）来致病，当糖类过量时，这种多糖会增强致龋性。单氟磷酸钠（MFP）是牙膏中一种具有活性的防龋化合物。在此，我们表明MFP可抑制（半数抑制浓度为1.5 mM）变形链球菌ADP - 葡萄糖焦磷酸化酶（EC 2.7.7.27），该酶催化IPS生物合成中的关键步骤。MFP对酶的抑制作用与正磷酸盐（Pi）相似，但不同的是，MFP所引起的效应不会像Pi那样被1,6 - 二磷酸果糖逆转。在用2 mM单氟磷酸钠培养的变形链球菌细胞中，抑制作用与产酸减少和IPS积累减少相关。这些效应不能被氟化钠模拟。鉴于糖原合成在哺乳动物和细菌中通过不同途径进行，ADP - 葡萄糖焦磷酸化酶可被视为控制变形链球菌毒力的分子靶点。我们的结果有力地表明，MFP是一种适合作用于该靶点的化合物，主要通过抑制IPS合成中的关键步骤来产生防龋效果。
