Selective Biofilm Inhibition\nthrough Mucin-Inspired\nEngineering of Silk Glycopolymers

Mucins are key components of innate immune defense and\npossess\nremarkable abilities to manage pathogenic microbes while supporting\nbeneficial ones and maintaining microbial homeostasis at mucosal surfaces.\nTheir unique properties have garnered significant interest in developing\nmucin-inspired materials as novel therapeutic strategies for selectively\ncontrolling pathogens without disrupting the overall microbial ecology.\nHowever, natural mucin production is challenging to scale, driving\nthe need for simpler materials that reproduce mucin’s bioactivity.\nIn this work, we generated silk-based glycopolymers with different\nmonosaccharides (GalNAc, GlcNAc, NeuNAc, GlcN, and GalN) and different\ngrafting densities. Using the oral cavity as a model system, we treated <i>in vitro</i> cultures of pathogenic Streptococcus\nmutans and commensal Streptococcus\nsanguinis with our glycopolymers, finding that silk-tethered\nGalNAc uniquely prevented biofilm formation without affecting overall\nbacterial growth of either species. This relatively simple material\nreproduced mucin’s virulence-neutralizing effects while maintaining\nbiocompatibility. These mucin-inspired materials represent a valuable\ntool for preventing infection-related harm and offer a strategy for\nthe domestication of pathogens in other environments.