Interactions of Streptococcus mutans in Supragingival Biofilms

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PROJECT SUMMARY / ABSTRACT The microbes that inhabit oral biofilms attached to the tooth’s surface are constantly involved in interactions with other microbes that impact their ability to survive and grow within their niche. Streptococcus mutans, a primary driver of dental caries (tooth decay) development, forms rotund microcolonies on the surfaces of teeth that are in contact with other commensal bacteria, particularly health-associated Streptococcus species that encode mechanisms to deter S. mutans emergence and initiation of the cariogenic cycle. Outgrowth of S. mutans leads to ecological shifts within the oral microbiome community, reducing the proportions of health- associated streptococci and instead promoting the outgrowth of other acidogenic and aciduric bacteria that then further drive the disease (caries) process. Therefore, describing the initial interactions that occur between S. mutans and commensals is of critical need in the field of oral health to begin understanding factors that influence S. mutans establishment, persistence and outgrowth. Discovering gene(s) and/or pathway(s) that could serve as potential therapeutic targets to thwart the appearance of Sm while keeping the normal, protective flora intact remains a favorable strategy towards caries prevention and overall maintenance of good oral health. Recently, our group described a novel gene expression pattern within S. mutans when it was grown in mixed-species cultures with health-associated streptococci. Interestingly, this gene expression pattern was consistent with multiple Streptococcus species, suggesting that this may be a common S. mutans- encoded response to these competitors. Our central hypothesis is that the mixed-species gene expression pattern provides a fitness benefit to S. mutans during the early stages of biofilm establishment and allows S. mutans to compete with health-associated commensals, particularly streptococci. Our objective is to first fully describe the S. mutans gene expression pattern during mixed-species growth with different groups of oral bacteria not currently tested, including health-associated non-Streptococcus species and disease (caries)- associated species. This will allow us to determine if the gene expression pattern observed previously is unique to health-associated streptococci or common during all S. mutans mixed-species interactions. We will then aim to determine if differentially-expressed genes, particularly up-regulated S. mutans genes previously identified and pre-selected through collected preliminary RNA-Seq data, provide a fitness benefit to S. mutans during mixed-species growth and whether these gene(s)/gene product(s) could serve as future therapeutic targets. We hypothesize that several S. mutans genes will emerge that will significantly modify S. mutans fitness in mixed-species interactions and/or significantly alter Sm rotund microcolony formation which are critical for the caries disease process. Together, these aims will advance our understanding of how S. mutans responds to intermicrobial competition, and whether we can leverage these interactions to design new strategies to prevent S. mutans emergence within the oral microbiome.