title: Monofluorophosphate Blocks Internal Polysaccharide Synthesis in Streptococcus mutans.
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.
authors.affiliation: Laboratorio de Enzimología Molecular, Instituto de Agrobiotecnología del Litoral (UNL-CONICET), Santa Fe, Argentina.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Demonte
authors.affiliation: Laboratorio de Enzimología Molecular, Instituto de Agrobiotecnología del Litoral (UNL-CONICET), Santa Fe, Argentina.
authors.forename: Matias D
authors.initials: MD
authors.lastname: Asencion Diez
authors.affiliation: Department of Chemistry and Biochemistry, Loyola University Chicago, Chicago, Illinois, United States of America.
authors.forename: Conrad
authors.initials: C
authors.lastname: Naleway
authors.affiliation: Laboratorio de Enzimología Molecular, Instituto de Agrobiotecnología del Litoral (UNL-CONICET), Santa Fe, Argentina.
authors.forename: Alberto A
authors.initials: AA
authors.lastname: Iglesias
authors.affiliation: Department of Chemistry and Biochemistry, Loyola University Chicago, Chicago, Illinois, United States of America.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Ballicora
mesh_terms: D003731:Dental Caries / Q000382:microbiology* / Q000517:prevention & control; D005459:Fluorides / Q000494:pharmacology*; D010710:Phosphates / Q000494:pharmacology*; D011135:Polysaccharides, Bacterial / Q000096:biosynthesis*; D012969:Sodium Fluoride / Q000494:pharmacology; D013295:Streptococcus mutans / Q000187:drug effects* / Q000378:metabolism; D014100:Toothpastes / Q000494:pharmacology*
chemical_list: D010710:Phosphates; D011135:Polysaccharides, Bacterial; D014100:Toothpastes; C012980:fluorophosphate; D012969:Sodium Fluoride; D005459:Fluorides