Advisory Committee Chair
Advisory Committee Members
Date of Award
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Dental caries, commonly known as tooth decay, is the most common infectious disease worldwide. The main etiological agent of dental caries is Streptococcus mutans which can readily form a biofilm on the surface of teeth and produce acids through the metabolism of dietary sugars, which is largely responsible for the demineralization and subsequent destruction of tooth enamel. In addition, S. mutans synthesizes extracellular glucosyltransferases (Gtfs) capable of breaking apart dietary sucrose and polymerizing the glucose subunits into the sticky glucan matrix of the biofilm, imperative for the formation of robust, three-dimensional biofilms. Currently used caries therapies are not species-specific and kill pathogenic species as well as commensals which are protective against the formation of pathogenic biofilms. There are several proteins in S. mutans whose function remains unknown but could present new targets for S. mutans specific anti-caries treatment. One such protein is a conserved, putative glycosyltransferase encoded by the gene smu_833 in S. mutans strain UA159. A homologue of SMU_833 in a different serotype of S. mutans, has been shown to glycosylate a surface collagen binding protein important for bacterial colonization in infective endocarditis. Thus, this protein makes a good candidate to be studied and analyzed for its potential as a target for caries therapies. In this study, we focused on elucidating the function of SMU_833 by understanding the role it plays in bacterial fitness and virulence. Deletion of smu_833 resulted in an altered biofilm matrix with significantly less glucan polysaccharide and increased eDNA. This mutation led to a less acidic biofilm and a decrease in colonization and cariogenicity in vivo. Further studies showed the smu_833 mutant was more susceptible to oxidative stress and less competitive against H2O2 producing oral streptococci. This was likely due to the decrease in the mutanobactin synthesizing complex uncovered by proteomics. Additionally, the mutant was found to have decreased expression of mutacin genes and lost the ability to inhibit commensal streptococci. Together, these data demonstrate the importance of SMU_833 in the fitness, virulence, and competitiveness of S. mutans. Our studies demonstrate SMU_833 represents a new target that can be used to develop potential anti-caries therapeutics.
Rainey, Katherine Lynn, "Determination of the role of SMU_833 in the fitness and virulence of cariogenic Streptococcus mutans" (2019). All ETDs from UAB. 2774.