Modulation of Lipoteichoic Acids and Exopolysaccharides Prevents Streptococcus mutans Biofilm Accumulation

Abstract

Dental caries is a diet–biofilm-dependent disease. Streptococcus mutans contributes to cariogenic biofilms by producing an extracellular matrix rich in exopolysaccharides and acids. The study aimed to determine the effect of topical treatments with compound 1771 (modulates lipoteichoic acid (LTA) metabolism) and myricetin (affects the synthesis of exopolysaccharides) on S. mutans biofilms. In vitro S. mutans UA159 biofilms were grown on saliva-coated hydroxyapatite discs, alternating 0.1% sucrose and 0.5% sucrose plus 1% starch. Twice-daily topical treatments were performed with both agents alone and combined with and without fluoride: compound 1771 (2.6 µg/mL), myricetin (500 µg/mL), 1771 + myricetin, fluoride (250 ppm), 1771 + fluoride, myricetin + fluoride, 1771 + myricetin + fluoride, and vehicle. Biofilms were evaluated via microbiological, biochemical, imaging, and gene expression methods. Compound 1771 alone yielded less viable counts, biomass, exopolysaccharides, and extracellular LTA. Moreover, the combination 1771 + myricetin + fluoride decreased three logs of bacterium counts, 60% biomass, >74% exopolysaccharides, and 20% LTA. The effect of treatments on extracellular DNA was not pronounced. The combination strategy affected the size of microcolonies and exopolysaccharides distribution and inhibited the expression of genes linked to insoluble exopolysaccharides synthesis. Therefore, compound 1771 prevented the accumulation of S. mutans biofilm; however, the effect was more pronounced when it was associated with fluoride and myricetin.

Compounds with Distinct Targets Present Diverse Antimicrobial and Antibiofilm Efficacy against Candida albicans and Streptococcus mutans, and Combinations of Compounds Potentiate Their Effect

“…A previous study with S. mutans using different concentrations of compound 1771 did not eliminate the bacterium [30], but the total elimination of CFU/mL count was observed here using the greatest concentration. In the same study [30], the antimicrobial activity of myricetin for S. mutans was at a lower concentration than the one found here. The antimicrobial effect of tt-farnesol on both species corroborates previous findings [18,22].…”

“…The formulations that combined agents with distinct targets prevented C. albicans and S. mutans dual-species biofilm build-up in vitro. The formulation C135+ tt -farnesol with or without fluoride may represent a potential alternative approach that deserves further investigation, including cytotoxicity to host [ 30 , 45 ]. Therefore, the outcomes of this study could be applied to future studies using the compound alone or combined as an adjuvant strategy to control oral biofilms using shorter exposure times, as mouthwashes.…”

“…The selected compounds and their concentrations were based on antimicrobial data: C135 (from 1250 to 62.5 µg/mL), myricetin (from 1250 to 125 μg/mL), tt -farnesol (from 1250 to 31.25 µg/mL), and compound 1771 (from 250 to 1.953 µg/mL). Previous studies evaluated the antibiofilm activity of myricetin, compound 1771, and tt -farnesol for S. mutans [ 18 , 19 , 30 ], but here distinct concentrations were tested. Tests with compound 1771 for C. albicans and C135 for both species will be presented for the first time.…”

“…The compound 1771 targets LtaS, an LTA synthase enzyme in S. aureus [ 28 ] and Enterococcus faecium [ 29 ]. This compound also hinders S. mutans biofilm formation [ 30 ]. However, the effect of compound 1771 on C. albicans is unknown.…”

Gram Positive Bacterial Lipoteichoic Acid Role in a Root Canal Infection – A Literature Review

“…Compound 1771 that modulates LTA metabolism inhibited Streptococcus mutants biofilm formation and this effect was more pronounced when it was used along with myrcitin and fluoride. 60…”