Using synthetic biology, an international team of researchers has uncovered how a novel microbial small molecule released by Streptococcus mutans is connected to the development of dental caries, offering new insights into the impact of the oral microbiome on systemic health and facilitating future research on the prevention of tooth decay.
Every wet surface on the planet is covered by biofilm made of microbial cells meshed in an extracellular organic matrix. An early National Institutes of Health study concluded that biofilm caused more than 80% of human bacterial infection. Thus, S mutans, which is a natural and primary inhabitant of the oral cavity that has a strong ability to form biofilms and produce organic acids, has long been acknowledged as the major etiological agent of dental caries.
Dental caries development is a complex process that mainly depends on the presence of microbial biofilms known as dental plaque on tooth surfaces. Also, tooth decay has been recognized as one of the most common bacterial infections and the cause of costly chronic conditions afflicting human beings. Annually, the global economic burden of treating tooth decay amounts to billions of dollars, the researchers said.
Although the macromolecular agents of S mutans for biofilm formation and development have been extensively investigated, the researchers said, the role of small-molecule secondary metabolites in the biofilm formation of S mutans remains largely unexplored.
The researchers have been studying the microbe-animal interactions mediated by signal molecules from biofilm using integrated genomics, transcriptomics, and chemical biology approaches. Recently, they have extended their work on biofilms to public health.
The researchers have discovered a polyketide/non-ribosomal peptide biosynthetic gene cluster, muf, which directly correlates with a strong biofilm-forming capability among S mutans strains clinically isolated from dental plaque. They also identified mutanofactin-697, a muf-associated bioactive product that includes a novel molecular scaffold.
Further mode-of-action studies revealed that this unique microbial secondary metabolite promotes biofilm formation via an unprecedented physiochemical mechanism, the researchers said. This small molecule binds to S mutans cells and extracellular DNA, increases bacterial hydrophobicity, and subsequently promotes bacterial adhesion and biofilm formation.
According to the researchers, their findings provide the first example of a microbial secondary metabolite that promotes biofilm formation via a physicochemical approach and highlight the significance of secondary metabolism in mediating critical processes related to the development of dental caries.
Also, the researchers said, this discovery will enable further mechanistic exploration of mutanofactin-related chemical regulatory processes in human oral ecology and streptococci-induced dental caries incidence and prevention.
The study, “Mutanofactin Promotes Adhesion and Biofilm Formation of Cariogenic Streptococcus Mutans,” was published by Nature Chemical Biology.