Mucus acts as a protective barrier on wet epithelial surfaces in the body including the gastrointestinal and reproductive tracts. A main component of mucus are mucins, which give mucus its viscoelastic properties and is a key component of host defense at these epithelial interfaces. Altered mucin production has been linked to gastrointestinal diseases such as Crohn's disease and respiratory illnesses like cystic fibrosis, which highlights the importance of regulated mucin production. Although mucins role in gastrointestinal and respiratory illnesses has been well characterized, little is known about the connection between salivary mucins and common oral diseases such as dental caries. Cavities form when bacteria attach to and grow on tooth surfaces then produce organic acids as metabolic byproducts, which dissolve tooth enamel. Streptococcus mutans is the primary cavity-forming oral bacterium, therefore understanding the impact of salivary mucins on S. mutans physiology may significantly impact the development of new oral therapies. In this study we will use a combination of microbiology, biochemistry, genetic and microscopy experiments to understand how human MUC5B salivary mucins affect S. mutans gene regulation and interaction with competing bacterial species. Preliminary data for this study shows that MUC5B increases survival of Streptococcus sanguinis, a beneficial oral bacterium known to compete with S. mutans, therefore we hypothesize that MUC5B plays a key role in decreasing the prevalence of caries and maintaining a healthy oral microbial community. To test this hypothesis we will first characterize differences in S. mutans gene regulation in the presence of MUC5B to understand the mechanism underlying mucins' protective influence. Then, we will evaluate the effects of MUC5B on S. sanguinis attachment and biofilm formation. Once we have determined the effects of MUC5B on key parameters of S. mutans and S. sanguinis physiology independently, we will use a dual-species model to understand how MUC5B impacts the development of multispecies biofilms. The main goals of this study are to understand how MUC5B influences S. mutans gene regulation then to determine how these changes play a role in inter-species bacterial competition. These findings could lead to significant insights into the pathogenesis of caries formation that aid in the development of novel therapies or preventative strategies.

Public Health Relevance

This research focuses on identifying the role of salivary mucins, natural defense molecules, in cavity formation. The application aims to determine how mucins impact gene regulation of common cavity-forming bacteria and how they influence bacterial competition in multispecies models. Understanding how mucins protect the oral cavity from common diseases, such as caries formation, could lead to breakthroughs in treatment and prevention.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
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NIDR Special Grants Review Committee (DSR)
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Frieden, Leslie A
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Harvard Medical School
Schools of Dentistry/Oral Hygn
United States
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Frenkel, Erica Shapiro; Ribbeck, Katharina (2017) Salivary mucins promote the coexistence of competing oral bacterial species. ISME J 11:1286-1290
Frenkel, Erica Shapiro; Ribbeck, Katharina (2015) Salivary mucins in host defense and disease prevention. J Oral Microbiol 7:29759