Tools of a pioneer colonizer

. Dental plaque is among the most complex microbial communities in humans, second only to the gastrointestinal tract. During community development, bacteria interact with and respond transcriptionally to proximal bacteria and host factors such as MUC5B. In this context, Streptococcus gordonii is a key model pioneer colonizer, transcriptionally discriminating MUC5B from a low-density salivary protein fraction using an outside-in signaling (OIS) circuit and also responding to Actinomyces naeslundii and other early plaque colonizers during coaggregation. We will learn whether OIS recognizes and responds to A. naeslundii polysaccharides and MUC5B and both together. The OIS circuit is comprised of recognition adhesin proteins known as SspA and SspB, lipoteichoic acid (LTA) for signaling across the cell wall into the membrane, and an intramembrane two-component system called SraSR for transcriptional regulation of adhesins sspA and sspB, tagatose pathway genes, and luxS (quorum sensing). Intramembrane C-terminal peptides (C-peps) cleaved from LPXTG-motif surface proteins by sortase A (SrtA) also modulate SraSR transcription, including adhesins as part of a larger transcriptional profile. Gaps to be addressed: S. gordonii interacts with some plaque species and competes with others, yet the vital role that pioneer S. gordonii plays in shaping the biofilm community and structure remains largely unknown. We seek to understand how the adhesin genes in the transcriptional responses of S. gordonii to other early plaque colonizers help shape the initial plaque community. Specifically, we aim to: 1. Examine the mechanism that S. gordonii uses to respond transcriptionally during co-aggregation with A. naeslundii. 2. Establish the structural basis and outcomes of interactions between the S. gordonii SspB adhesin V-region and A. naeslundii polysaccharides. 3. Characterize how OIS signaling influences the assembly of a synthetic oral bacterial community. Community changes in response to stressors may affect plaque composition and biogeography and underlie the transition from health to significant diseases of the oral cavity ranging from dental caries and periodontitis to squamous cell carcinoma. Given the burden and concomitant costs of disease that occur with unchecked changes in the composition of oral biofilms, our proposed research project will provide a better understanding of fundamental adhesive mechanisms that direct the membership and architecture of dental plaque and suggest novel targets for potential therapeutic interventions. Project Number: 1R01DE035108-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Dental and Craniofacial Research (NIDCR) | Principal Investigator: MARK HERZBERG | Institution: UNIVERSITY OF MINNESOTA, MINNEAPOLIS, MN | Award Amount: $649,046 | Activity Code: R01 | Study Section: Oral, Dental and Craniofacial Sciences Study Section[ODCS] View on NIH RePORTER: https://reporter.nih.gov/project-details/11361779