In a preclinical model, University of Alabama at Birmingham (UAB) researchers have created a small molecule that prevents or impedes dental caries by inhibiting Streptococcus mutans from colonizing oral biofilm. This molecular inhibitor reduced the incidence of caries in rats fed a cariogenic diet, according to the study, “Structure-Based Discovery of Small Molecule Inhibitors of Cariogenic Virulence,” published in Scientific Reports.
Using computer simulations, the team studied the crystal structure of S. mutans glucosyltransferase, or Gtf, enzymes to screen 500,000 drug-like compounds for binding at the enzyme’s active site. Of the 90 compounds tested for their ability to block biofilm formation by S. mutans, seven showed potent, low-micromolar inhibition; in particular, the #G43 compound proved very promising and underwent more extensive testing.
Using a rat model, subjects were infected with S. mutans and the teeth were treated topically with #G43 twice a day for four weeks. The #G43 treatment caused what the team described as significant reductions in enamel and dentinal caries. “Successful development of this selective lead inhibitor offers proof of concept that targeting keystone bacteria holds promise for the design of new therapies,” notes lead investigator Hui Wu, PhD, a professor of pediatric dentistry at UAB School of Dentistry and director of the UAB Microbiome Center.