This summer, Dr. Grace Spatafora, professor of biology department, was awarded a $2.1 million National Institutes of Health grant for her research on the oral bacterium, Streptococcus mutans. The grant makes her one of only 13 faculty members at small liberal arts colleges nationwide to receive an NIH research project grant, known as an RO1 grant. The majority are awarded to large research-intensive universities.
Streptococcus mutans is a bacterium that lives in the oral cavity, where it is the primary cause of dental cavities. Although S. mutans can promote cavities as well as contribute to the progression of periodontal disease, it is a natural part of our oral microbiome and is just as vital to our health as our gut microbiome.
Oral health is generally considered the gateway to overall health; a diseased mouth can have dire consequences for the rest of the body.
“The condition of one’s mouth says a lot about where that person is on the socioeconomic scale and what kind of overall health they’re in. If we can improve access to oral health and hygiene practices for all, then we can improve general health and lessen the gap between the haves and the haves-not,” Spatafora said.
S. mutans adheres to teeth and metabolizes carbohydrates consumed in the diet via the process of fermentation. Acid, a product of fermentation, drills holes in teeth, marking the onset of tooth decay. There is, however, a difference between healthy plaque and diseased plaque.
Spatafora describes her research as “centered on the genetic mechanisms that help maintain healthy plaque, and which involves a delicate balance between healthy microbes and disease-causing microbes.”
Maintaining the healthy plaque requires multiple factors including healthy diet and good oral hygiene. The high sugar content of the Western diet, however, provides S. mutans with an abundance of nutrients that get converted to acid. This acid production lowers the pH in the mouth, tipping the balance in favor of diseased plaque with a prevalence of acid-producing and acid-tolerant microbes.
To understand how we might be able to control this delicate homeostasis, Spatafora’s lab is examining SloR, a protein in S. mutans that is responsible for the regulation of metal ion transport. “By restricting access of S. mutans to essential metals, such as manganese and iron, [SloR] receives neither too many micronutrients nor too few, keeping its prevalence in the mouth in check.”
For example, when we eat, our food introduces large amounts of manganese and iron into the mouth, in addition to sugar. S. mutans can absorb these metal ions through membrane-associated transporters, thereby allowing SloR to interact with the ions. The interaction permits SloR to bind to DNA and repress an excess of metal ion uptake, which could otherwise be toxic for the S. mutans. At the same time, SloR-metal ion complexes modulate the damaging characteristics of S. mutans, such as its ability to adhere to teeth, produce acid, and resist the negative effects of acid and oxidative stress.
“By manipulating SloR-metal ion complexes and their interaction with DNA, we can also manipulate the disease-causing potential of S. mutans,” Spatafora said.
Ultimately, Spatafora hopes to “develop a therapeutic intervention that will target SloR so that S. mutans-induced cavities can be alleviated or prevented altogether.”
Spatafora first started working on S mutans in 1989 after pursuing her interest in infectious diseases and microbial pathogenesis in Dr. Roy Curtiss’ laboratory at Washington University in St. Louis. There, Curtiss introduced her to S. mutans, a bacterium that not many people were working with at the time. She was drawn to the microorganism because of the opportunities it provided for experimental manipulation and the ability to work on this project with a small group of graduate students and highly trained post-docs.
Now, Spatafora offers incredible research opportunities to Middlebury students such as Annie Cowan ’18.
“Professor Spatafora wants you to lead your own project and so you end on the same level in terms of knowing where the project is going and what to do in terms of moving forward. I think the most rewarding part is identifying where your mistake is yourself and then figuring out how to fix it,” said Cowan of her time working in Spatafora’s lab.
Cowan has been working on a project verifying a region of DNA that could promote synthesis of SloR. The region was identified last year by Patrick Monette ’17, who is currently preparing a manuscript about the findings, in hopes of being published.
Another of Spatafora’s lab students, Sunho Park ’18 (known as the lab clown), has been conducting experiments to find protein binding partners of SloR.
Park says, “Once we know what other proteins it binds to, then maybe we can investigate the binding partners, which would allow us to learn more about SloR indirectly from a different angle,” Park said.
Hopefully, this could one day allow us to utilize SloR to maintain the homeostasis of our mouths and lead to preventing cavities.
Thanks to the five-year National Institutes of Health grant, students of the college will continue to receive funding for these extraordinary research opportunities through 2022.
