It has recently been recognized that microorganisms can produce functional amyloids that are integral to bio-film development. We have found that amyloid is present in human dental plaque and is produced by both laboratory strains and clinical isolates of S. mutans, an established etiologic agent of human dental caries. The P1 adhesin (aka Antigen I/II or PAc) is a cell surface-localized protein involved in sucrose-independent adhesion and colonization of the tooth surface. The immuno-reactive and adhesive properties of S. mutans suggest an unusual functional quaternary ultrastructure comprised of intact P1 covalently attached to the cell wall and interacting with non-covalently associated proteolytic fragments thereof, particularly the ~57-kDa C-terminal fragment C123 previously identified as Antigen II. P1 is also among the amyloidogenic proteins of S. mutans and the C123 fragment of P1 readily forms amyloid fibers in vitro suggesting it may play a role in the formation of functional amyloid during biofilm development. Using NMR spectroscopy, we have characterized the specific binding of C123 to P1 on intact cell walls as well as the biologically relevant interactions of the individual C3 domain with A3VP1, a polypeptide that represents the apical head of P1 as it is projected on the cell surface. We have also evaluated C3’s interaction with C12 and the adhesion-inhibiting monoclonal antibody (MAb) 6-8C. Together these results identify a specific C3-A3VP1interaction that serves as a foundation for understanding the interaction of C123 with P1 on the bacterial surface and the related biological processes that stem from this interaction. Additionally, we have measured the interaction of epigallocatechin-3-gallate (EGCG) and resveratrol (RSV) with C123 and C3 domains at physiologic pH using WaterLOGSY experiments. We are now turning our attention to characterizing the structures of C123 fibrils via MAS DNP NMR spectroscopy. Together these studies highlight the roles of quaternary interactions and structural transitions underlying functional amyloid formation and provide insights for developing inhibitors of biofilm formation.

Functional amyloid formation in Streptococcus mutans

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.