Abstract

Mucins are key components of innate immune defense and possess remarkable abilities to manage pathogenic microbes while supporting beneficial ones and maintaining microbial homeostasis at mucosal surfaces. Their unique properties have garnered significant interest in developing mucin-inspired materials as novel therapeutic strategies for selectively controlling pathogens without disrupting the overall microbial ecology. However, natural mucin production is challenging to scale, driving the need for simpler materials that reproduce mucin's bioactivity. In this work, we generated silk-based glycopolymers with different monosaccharides (GalNAc, GlcNAc, NeuNAc, GlcN, and GalN) and different grafting densities. Using the oral cavity as a model system, we treated in vitro cultures of pathogenic Streptococcus mutans and commensal Streptococcus sanguinis with our glycopolymers, finding that silk-tethered GalNAc uniquely prevented biofilm formation without affecting overall bacterial growth of either species. This relatively simple material reproduced mucin's virulence-neutralizing effects while maintaining biocompatibility. These mucin-inspired materials represent a valuable tool for preventing infection-related harm and offer a strategy for the domestication of pathogens in other environments.