An electron microscope image showing clumps of Streptococcus mutans, strains of which are the dominant cavity-causing bacteria in humans. The bacteria form clumps after producing and secreting a molecule discovered by UC Berkeley researchers. This and another newly discovered molecule help bacteria form biofilms on teeth, where some bad actors secrete acids that eat away at tooth enamel and promote cavities.
McKenna Yao/UC Berkeley
If Wenjun Zhang has her way, no one will ever have to brush or floss again.
Zhang, a UC Berkeley professor of chemical and biomolecular engineering, is trying to distinguish the healthy bacteria in our mouths from the unhealthy bacteria — those that cause cavities — so that she can boost the proportion of the former and promote a probiotic oral microbiome.
Our mouth’s microbiome consists of hundreds of different species of bacteria, many of which form a community that sticks to teeth to form plaque. Previous studies have focused on which of those species are associated with cavities, producing acid that eats away at tooth enamel. But researchers have found that each species is not uniformly good or bad — individual species can have hundreds of different varieties, called strains, that differ in their cavity-promoting qualities.
Instead of focusing on species or strains, Zhang and her team scan the DNA sequences of all the bacteria in the mouth — the metagenome — in search of clusters of genes associated with cavities.
In a paper published Aug. 19 in the journal Proceedings of the National Academy of Sciences, she and her colleagues reported the discovery of one such gene cluster that produces two molecules that together help the mouth’s community of bacteria — good and bad — stick together and form a strong biofilm on teeth.
A graphic showing how two different small molecules (blue and pink) made by bacteria in the mouth help oral bacteria (yellow) form strands and clumps, respectively, in a biofilm that sticks to teeth. One known cavity-causing bacteria, Streptococcus mutans (right), contains a cluster of genes that makes these molecules. Mapping the many molecules synthesized by oral bacteria may pinpoint gene clusters that can help the good bacteria in the mouth out-compete the bad and prevent cavities.
Wenjun Zhang and McKenna Yao/UC Berkeley
They found this gene cluster in some but not all strains of several known bad actors in the mouth, including Streptococcus mutans — the main villain in tooth decay. Zhang sees an opportunity to stick this gene cluster into good bacteria to help them attach better to teeth and push out the acid-producing bacteria that pave the way for cavities.
“Particular strains belonging to the same species can be a pathogen or a commensal or even probiotic,” Zhang said. “After we better understand these molecules’ activity and how they can promote strong biofilm formation, we can introduce them to the good bacteria so that the good bacteria can now form strong biofilms and outcompete all the bad ones.”
The work was supported by the National Institute of Dental & Craniofacial Research of the National Institutes of Health (R01DE032732).
“Specialized” metabolism
The gene cluster was discovered by searching through an online database of a large number of metagenomic sequences of the microbial communities in the mouths of human volunteers. Berkeley graduate student McKenna Yao conducted a statistical analysis to identify clusters associated with oral disease and then cultivated the bacteria to analyze and identify the metabolites produced by these clusters.
At left, an electron microscope image of a biofilm formed by two newly discovered molecules synthesized by bacteria in the mouth. At right, a closeup of the cells that form the biofilm, showing both strands and clumps of bacteria — each made possible by a different type of mutanoclumpin. Such biofilms help bacteria, both good and bad, stick to teeth.
Wenjun Zhang and McKenna Yao/UC Berkeley
The metabolites are small molecules composed of short strands of amino acids — peptides — and fatty acids, or lipids. One molecule works like glue, helping cells clump together into blobs, while the other acts more like string, letting them form chains. Together they give bacteria the ability to build communities — the sticky substance on your teeth — instead of floating alone.
The newfound gene cluster contains about 15 DNA segments coding for proteins, enhancers and transcription factors that act like a self-contained metabolic cassette — an alternative metabolic pathway that is not essential for survival of the bacteria but which, Zhang has found, has major impacts on the surrounding environment, such as teeth. These gene clusters are sometimes referred to as a microbe’s secondary metabolism, but Zhang prefers the term “specialized” because they can produce interesting molecules. Specialized metabolic networks in soil bacteria have proved a fertile source of antibiotics, for example.
