If Wenjun Zhang has its way to her way, no one should ever brush or come back.
Zhang, a professor of chemical and biomolecular engineering of Berkeley, tries to distinguish healthy bacteria in our mouths from unhealthy bacteria – those that cause cavities – so that it can enhance the percentage of the former and promote a probiotic oral microbicides.
Our mouth microbialicide consists of hundreds of different types of bacteria, many of which form a community that sticks to the teeth to form plaque. Previous studies have focused on which of these species are associated with cavities, producing acid that eats away in the tooth enamel. But researchers have found that each species are not even good or bad – individual species can have hundreds of different varieties, called strains, which differ in the properties that promote the cavity.
Instead of focusing on species or strains, Zhang and its group scan DNA sequences of all bacteria in the mouth – the metagonide – looking for bacterial clusters associated with cavities.
In a document published on August 19th in the magazine Proceedings of the National Academy of SciencesShe and her colleagues mentioned the discovery of such a gene complex that produces two molecules that together help the bacteria of the mouth – well and bad – to stick together and form a strong biofilm in the teeth.
Found this gene complex in some but not all the executives of many known bad actors in the mouth, including Streptococcus Mutans – The main villain in tooth decay. Zhang sees the opportunity to stick this gene complex to good bacteria to help them attach better to the teeth and push the bacteria that produce acids that pave the way for the cavities.
Specific strains belonging to the same species may be pathogenic or ordinary or even probiotic. After better understanding the activity of these molecules and how they can promote the strong biofilm formation, we can introduce them to good bacteria so that good bacteria can now form strong biofilm and overcome all the bad. “
Wenjun Zhang, Professor of Chemical and Biomological Engineering, UC Berkeley
The project was supported by the National Institute of Dental & Craniophilic Research of the National Institutes of Health (R01DE032732).
“Specialized” metabolism
The gene complex was discovered by searching through an online database of a large number of metagonal sequences of the microbial communities in the mouths of human volunteers. Berkeley McKenna Yao’s postgraduate student conducted a statistical analysis to identify clusters related to oral disease and then cultivated the bacteria to analyze and recognize the metabolites produced by these clusters.
Metabolites are small molecules consisting of small strands of amino acids – peptides – and fatty acids or lipids. A molecule works like glue, helping cells to accumulate together in spots, while others act more like string, letting them form chains. Together they give the bacteria the ability to make communities – the sticky substance in your teeth – instead of floating on their own.
The new gene complex contains about 15 DNA segments encoding proteins, amplifiers and transcription factors that act as autonomous metabolic cartridge – an alternative metabolic pathway that is not necessary for the survival of bacteria, but that Zhang has found, such as the significant effects on the environment. These gene groups are sometimes referred to as secondary metabolism of the germ, but Zhang prefers the term “specialized” because it can produce interesting molecules. Specialized metabolic networks in soil bacteria have proven to be a fertile source of antibiotics.
“These specialized metabolites enhance survival in some ways,” said Yao, one of Berkeley’s three postgraduate students who contributed to the project and are the first authors of the document. “Many, for example, are antibiotics so that they can kill other errors or others are involved in acquiring metals – they help bacteria monopolize resources in their environmental position.
However, the role of specialized metabolic networks and secondary metabolites in human microbicide remained largely unjustified, Zhang said. Two years ago, her colleagues found a gene complex in mouth bacteria that produces a previously unknown antibiotic. They found another gene complex that produced a different set of molecules that help create biofilm.
The newly formed gene complex is another demonstration of the importance of secondary metabolites of the germ in human health, either in the mouth, in the intestine, in the skin or in any organ. Understanding these sticky metabolites in the mouth, called Mutanoclumpins, could help reduce cavities.
“We are looking for something that is associated with the cavities, with illness, if one day we can prove that, under certain conditions, this is really a bad molecule you want to prevent, we could develop genetic or chemical inhibitors to inhibit their production, so we hope that “In the meantime, we also look at other health -related molecules, allowing a simple strategy to directly design germs to make more of them.”
A kind of bacteria that could use push is Streptococcus Salivariuswhich seems to promote oral health and today is commercially available as an oral probiotic. Unfortunately, even if proven probiotic, it does not form a powerful biofilm that sticks to the teeth and quickly dissolves. Zhang suggests the addition of strong biofilm formation molecules to S. Salivario To see if bacteria can work better as probiotics.
“Our future job will be to create a wide map of the collection of these specialized metabolites to collectively look at what this dynamic, complex community in your teeth is doing,” Zhang said.
Yao, however, noted that “the best way you can remove biofilm in your teeth is to brush. We believe there is really a better way to disturb this biofilm, but we begin to understand what the complexity in the mouth is.”
Nicholas Zill and Colin Charles Barber are first co-authors with Yao. Other co-authors are Yongle Du, Rui Zhai, Eunice Yoon and Dunya Al Marzooqi of Berkeley’s Department of Chemicals and Bi-Companions and Peijun Lin, a visiting student at the College of Computing, Science Science and Society.
Source:
Magazine report:
Yao, ml, et al. (2025). Symphony of specialized metabolites from divergent biosynthesis in human oral microbicide. Proceedings of the National Academy of Sciences. Doi.org/10.1073/pnas.2504492122