Preventing Tooth Cavities with an Inhibitor

Researchers at the University of Alabama at Birmingham have created a small molecule that prevents tooth cavities in a preclinical model. The inhibitor blocks the function of an enzyme in an oral bacterium and prevents it from forming biofilms. Specifically the inhibitor causes Streptococcus mutans (S. mutans) which is the prime bacterium that causes tooth decay and dental cavities, to not make the sticky bioflim that has it glue to a tooth surface. The selective inhibition of the sticky biofilm acts against S. mutans reduced dental caries in rats fed a diet intended to promote cavities.

The glucan biofilm is made by three S. mutans glucosyltransferase (Gtf) enzymes. It is know what the crystal structure of the GtfC glucosyltransferase is, and the researchers used the structure to run numerous computer simulations for drug-like compounds for binding at the enzyme’s active site. Ninety compounds with diverse scaffolds that showed promise in the computer simulations were purchased and tested for their ability to block biofilm formation by S. mutans. Seven were found to show the most promise. The researchers further narrowed their candidate to #G43 which inhibited the activity of enzymes GtfB and GtfC. #G43 did not inhibit the expression of the gtfC gene, and did not affect growth of S. mutans and other oral bacteria. #G43 also was found to not inhibit biofilm production by several oral streptococcal species.

The researchers fed rats a low-sucrose diet and infected them with S. mutans. The rats teeth were treated topically with #G43 twice a day for four weeks. The #G43 treatment was found to cause large  reductions in tooth enamel and cavities. The researchers feel that their compound can be developed into drugs that prevent and treat dental cavities.  Development of the inhibitor in the dental setting offers a proof of concept that selective targeting of key bacteria may help with new treatment approaches. This may serve to be more beneficial to many than the common approach today of tooth brushing and flossing to remove oral bacteria.

Source: Qiong Zhang and et. al., Structure-Based Discovery of Small Molecule Inhibitors of Cariogenic Virulence. Scientific Reports, vol. 7, issue 1, 2017.

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