New Research Sheds Light on How Plaque Biofilm Forms

We’ve long understood that Streptococcus mutans is the primary miscreant in the tooth decay scenario. But an international team of researchers using a synthetic biology approach has drilled down further into the mechanics of this interaction, revealing a link between dental caries development and a novel microbial small molecule released by S mutans.¹ The findings also offer insights into how the human oral microbiota impacts overall systemic health.

BIOFILM

Biofilm is a fact of nature wherever there is a wet surface. Early studies conducted by the National Institutes of Health found that more than 80% of human bacterial infections were caused by biofilm. S. mutans easily forms biofilms, or plaque, and produces organic acids. These play a major role in the development of dental caries, which is seen as one of the most common bacterial infections in humans. As a chronic problem, caries can prove both painful and costly.

But while S. mutans has long been investigated for its role in biofilm formation and caries etiology, the role played by the small-molecule secondary metabolites it releases has not. Until now.

Researchers from the Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou) and Hong Kong University of Science and Technology had been using integrated approaches from genomics, transcriptomics, and chemical biology to study the microbial interactions mediated by biofilm signal molecules.¹ Recently, however, the team extended its work on biofilms to include those related to public health.

The Hong Kong investigators collaborated with researchers from the University of California at Berkeley and University of Florida College of Dentistry to work with S. mutans strains that were clinically isolated from dental plaque. They discovered a new polyketide/nonribosomal peptide biosynthetic gene cluster (muf) that influences the biofilm-forming capabilities of S. mutans. 

Subsequently, the researchers identified the muf-associated bioactive product, mutanofactin-697, which contains a novel molecular scaffold. Further studies revealed that this unique microbial secondary metabolite promotes biofilm formation via a unique physicochemical mechanism, facilitating initial surface adhesion and cell-to-cell aggregation. 

TIES THAT BIND

It turns out that this small molecule binds to S. mutans cells nonspecifically, modifying bacterial surface physicochemical properties and promoting self-aggregation of bacterial cells and biofilm formation in a dose-dependent manner. It increases bacterial hydrophobicity, promoting bacterial adhesion and, ultimately, biofilm formation.

The study delivers the first example of a microbial secondary metabolite promoting biofilm formation through a physicochemical approach. Such a finding underscores the significance of a secondary metabolism in mediating critical processes related to the development of dental caries and facilitates future research into its prevention.

In that respect, there are several dental aids and strategies that can be deployed to disrupt biofilm formation on oral structures. From the regular use of floss and interdental brushes for all tooth surfaces to antimicrobial agents and regular dental hygiene appointments—to futuristic employment of microrobots, keeping teeth free of plaque isn’t mission impossible.

Reference

1. Li ZR, Sun J, Du Y, et al. Mutanofactin promotes adhesion and biofilm formation of cariogenic Streptococcus mutans. Nat Chem Biol. 2021 Mar 4.