Probing the role of Selenomonas sputigena in supragingival biofilm spatial structuring and virulence

About This Grant

The R00 phase will establish an independent laboratory to complete the planned studies on how Selenomonas sputigena (Ss), a motile oral bacterium strongly associated with early childhood caries (ECC), colonizes tooth surfaces and organizes with Streptococcus mutans (Sm) to promote virulent, spatially structured biofilms. ECC remains a major public health problem driven by biofilm formation under sugar-rich conditions, leading to rampant tooth decay and systemic complications in children. The long-term objective is to identify motility-driven mechanisms of supragingival biofilm virulence that can be targeted to reduce ECC burden. The central hypothesis is that Ss motility modulates early surface colonization and mixedspecies structuring with Sm, generating localized acidogenic niches that exacerbate enamel demineralization. To test this hypothesis, the project will 1) characterize Ss motility in relation to surface colonization and biofilm initiation under conditions relevant to the oral environment; 2) determine the spatiotemporal assembly of S~Sm biofilms and site-specific gene expression using single-cell and in situ transcriptomics integrated with local pH mapping and enamel demineralization readouts; and 3) investigate Ss-mediated colonization, interspecies spatial structuring/omics and biofilm virulence in vivo while assessing strategies that disrupt motility-modulated assembly. High-speed live imaging with quantitative trajectory analysis will define motility and colonization behaviors, while single-cell and spatial transcriptomics will resolve localized transcriptional states and an established rodent caries model will connect spatial organization to disease severity. The expected outcome is a mechanistic framework linking motility to cariogenic function and actionable targets for prevention. In addition, it will provide a platform to study other motile oral bacteria in health and disease, which remain understudied, and position the laboratory for sustained, independent investigation and future R01-level studies.