Antibacterial activity of disodium succinoyl glycyrrhetinate, a derivative of glycyrrhetinic acid against Streptococcus mutans

Microbiol Immunol. 2019 Jul;63(7):251-260. doi: 10.1111/1348-0421.12717. Epub 2019 Jun 29.

Abstract

Streptococcus mutans is a cariogenic bacterium that localizes in the oral cavity. Glycyrrhetinic acid (GRA) is a major component of licorice extract. GRA and several derivatives, including disodium succinoyl glycyrrhetinate (GR-SU), are known to have anti-inflammatory effects in humans. In this study, the antimicrobial effect of GRA and its derivatives against the S. mutans UA159 strain were investigated. Minimum inhibitory concentrations (MICs) of GRA and GR-SU showed antibacterial activity against the S. mutans strain, whereas other tested derivatives did not. Because GR-SU is more soluble than GRA, GR-SU was used for further experiments. The antibacterial activity of GR-SU against 100 S. mutans strains was evaluated and it was found that all strains are susceptible to GR-SU, with MIC values below 256 µg/mL. A cell viability assay showed that GR-SU has a bacteriostatic effect on S. mutans cells. As to growth kinetics, sub-MICs of GR-SU inhibited growth. The effect of GR-SU on S. mutans virulence was then investigated. GR-SU at sub-MICs suppresses biofilm formation. Additionally, GR-SU greatly suppresses the pH drop caused by the addition of glucose and glucose-induced expression of the genes responsible for acid production (ldh and pykF) and tolerance (aguD and atpD). Additionally, expression of enolase, which is responsible for the carbohydrate phosphotransferase system, was not increased in the presence of GR-SU, indicating that GR-SU suppresses incorporation of sugars into S. mutans. In conclusion, GR-SU has antibacterial activity against S. mutans and also decreases S. mutans virulence.

Keywords: Antibacterial agent; Streptococcus mutans.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Biofilms / drug effects
  • Biofilms / growth & development
  • Gene Expression Regulation, Bacterial / drug effects
  • Genes, Bacterial / genetics
  • Glucose / metabolism
  • Glycyrrhetinic Acid / chemistry
  • Glycyrrhetinic Acid / pharmacology*
  • Glycyrrhiza / chemistry*
  • Hydrogen-Ion Concentration
  • Microbial Sensitivity Tests
  • Microbial Viability / drug effects
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Streptococcus mutans / drug effects*
  • Streptococcus mutans / genetics
  • Streptococcus mutans / growth & development
  • Virulence
  • Virulence Factors / genetics
  • Virulence Factors / metabolism

Substances

  • Anti-Bacterial Agents
  • Plant Extracts
  • Virulence Factors
  • Glucose
  • Glycyrrhetinic Acid