Glucosyltransferase Inactivation Reduces Dental Caries

Abstract

Dental caries has been an intractable disease in spite of intense dental research. The metabolic acids produced by mutans streptococci demineralize the tooth surface and lead to dental caries. The enzyme glucosyltransferase (GTF) produced by mutans streptococci is the key factor in this process. Oral bacterial GTFs use sucrose as a substrate in synthesis of either water-soluble or insoluble glucans. In this investigation, kinetic studies with divalent metal ions revealed their strong binding affinity to GTF. The metal ions also proved to be strong inhibitors of the enzyme. Here we describe a simple method of inactivating the enzyme that actively participates in dental caries by taking advantage of a Fenton reaction which requires metal ions such as iron or copper and peroxide. The hydroxyl radical ions produced via the Fenton reaction inactivate GTF, a factor in the production of dental caries.

The effect of iron on Streptococcus mutans biofilm and on enamel demineralization

“…7 On the other hand, the mechanism for this effect does not seem to be related to inhibition of EPS production by S. mutans GTFs. 12,13 Like prior in situ dental biofilm findings, 7 our results suggest that the reduction in demineralization cannot be explained by a direct effect on GTF activity. This absence of an effect on EPS production by S. mutans in the biofilm also cannot be explained based on the concentration of Fe used in this experiment, since at the highest concentration used (100 µg/mL = 1.8 mM), 80% EPS inhibition, found in previous in vitro studies, 13 would have been expected.…”

“…12,13 Like prior in situ dental biofilm findings, 7 our results suggest that the reduction in demineralization cannot be explained by a direct effect on GTF activity. This absence of an effect on EPS production by S. mutans in the biofilm also cannot be explained based on the concentration of Fe used in this experiment, since at the highest concentration used (100 µg/mL = 1.8 mM), 80% EPS inhibition, found in previous in vitro studies, 13 would have been expected. The lack of EPS inhibition suggests that reduction in demineralization cannot be explained by a specific oxidative effect via the Fenton reaction in the amino acid residues of the active site of GTFs, as Devulapall and Mooser 13 have suggested.…”

“…This absence of an effect on EPS production by S. mutans in the biofilm also cannot be explained based on the concentration of Fe used in this experiment, since at the highest concentration used (100 µg/mL = 1.8 mM), 80% EPS inhibition, found in previous in vitro studies, 13 would have been expected. The lack of EPS inhibition suggests that reduction in demineralization cannot be explained by a specific oxidative effect via the Fenton reaction in the amino acid residues of the active site of GTFs, as Devulapall and Mooser 13 have suggested. In fact, in the Fenton reaction, Fe reacts with H 2 O 2 to form a hydroxyl radical (OH·), which is a nonspecific oxidizing agent that provokes irreversible changes in all proteins.…”

“…11 Moreover, it has been shown that Fe inhibits glycotransferase (GTF) enzymes produced by S. mutans in vitro 12 via an oxidative mechanism involving a Fenton-type reaction. 13 However, Fe at a concentration of 70 µg/mL (1.2 mM) has shown no in situ effect either on the acidogenicity of dental biofilm or in terms of reducing the quantity of EPS in a biofilm exposed to 10% sucrose, 7 thus suggesting the need for further studies on the mechanism of action of the anticaries effect of Fe.…”

Evaluation of the Effect of Ferrous Sulfate on Enamel Demineralization of Human Deciduous Teeth: An in Vitro Study

“…Iron supplements are well tolerated by most infants, have no measurable effect on body growth in children, and early iron supplementation, even in breastfed infants, is feasible and transiently increases iron status 4 . FS has been analyzed in several studies in dentistry [5][6][7][8][9][10][11][12][13] using artificial dental models (mainly bovine teeth and human permanent teeth). The most frequently reported properties include reduction in the degree of enamel dissolution 5,8,13 , reduction of dental erosion 7,12 , alterations in biofilm composition (in situ) 9,10,14 , and oxidative modifications in glucosyltransferase promotion 11 .…”