Selective Biofilm Inhibition through Mucin-Inspired Engineering of Silk Glycopolymers

IF 14.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Caroline Andrea Werlang, Jugal Kishore Sahoo, Gerado Cárcarmo-Oyarce, Corey Stevens, Deniz Uzun, Rachel Putnik, Onur Hasturk, Jaewon Choi, David L. Kaplan, Katharina Ribbeck
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引用次数: 0

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.

Abstract Image

通过粘蛋白启发工程的丝绸糖共聚物选择性生物膜抑制
粘蛋白是先天免疫防御的关键组成部分,具有控制致病微生物的同时支持有益微生物和维持粘膜表面微生物稳态的卓越能力。它们的独特性质引起了人们对开发黏液激发材料的极大兴趣,作为选择性控制病原体而不破坏整体微生物生态的新型治疗策略。然而,天然粘蛋白的生产规模具有挑战性,这推动了对更简单的材料的需求,以复制粘蛋白的生物活性。在这项工作中,我们用不同的单糖(GalNAc、GlcNAc、NeuNAc、GlcN和GalN)和不同的接枝密度制备了基于丝绸的糖共聚物。以口腔为模型系统,我们用我们的糖共聚物处理致病性变形链球菌和共生血性链球菌的体外培养,发现丝系GalNAc独特地阻止了生物膜的形成,而不影响两种细菌的整体生长。这种相对简单的材料在保持生物相容性的同时复制了粘蛋白的毒力中和作用。这些黏液激发的材料代表了预防感染相关伤害的宝贵工具,并为在其他环境中驯化病原体提供了一种策略。
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来源期刊
CiteScore
24.40
自引率
6.00%
发文量
2398
审稿时长
1.6 months
期刊介绍: The flagship journal of the American Chemical Society, known as the Journal of the American Chemical Society (JACS), has been a prestigious publication since its establishment in 1879. It holds a preeminent position in the field of chemistry and related interdisciplinary sciences. JACS is committed to disseminating cutting-edge research papers, covering a wide range of topics, and encompasses approximately 19,000 pages of Articles, Communications, and Perspectives annually. With a weekly publication frequency, JACS plays a vital role in advancing the field of chemistry by providing essential research.
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