Nepravishta Ridvan, Monaco Serena, Distefano Marco, Rizzo Roberto, Cescutti Paola, Angulo Jesus
School of Pharmacy, University of East Anglia, Norwich, United Kingdom.
Department Life Sciences, University of Trieste, Trieste, Italy.
Front Mol Biosci. 2021 Sep 16;8:727980. doi: 10.3389/fmolb.2021.727980. eCollection 2021.
Biofilms confine bacterial cells within self-produced matrices, offering advantages such as protection from antibiotics and entrapment of nutrients. Polysaccharides are major components in these macromolecular assemblies, and their interactions with other chemicals are of high relevance for the benefits provided by the biofilm 3D molecular matrix. NMR is a powerful technique for the study and characterization of the interactions between molecules of biological relevance. In this study, we have applied multifrequency saturation transfer difference (STD) NMR and DOSY NMR approaches to elucidate the interactions between the exopolysaccharide produced by C1576 (EpolC1576) and the antibiotics kanamycin and ceftadizime. The NMR strategies presented here allowed for an extensive characterization at an atomic level of the mechanisms behind the implication of the EpolC1576 in the recalcitrance phenomena, which is the ability of bacteria in biofilms to survive in the presence of antibiotics. Our results suggest an active role for EpolC1576 in the recalcitrance mechanisms toward kanamycin and ceftadizime, though through two different mechanisms.
生物膜将细菌细胞限制在自身产生的基质中，具有如抵御抗生素和截留营养物质等优势。多糖是这些大分子聚集体的主要成分，它们与其他化学物质的相互作用对于生物膜三维分子基质所提供的益处至关重要。核磁共振（NMR）是研究和表征具有生物学相关性的分子间相互作用的强大技术。在本研究中，我们应用多频饱和转移差（STD）NMR和扩散排序谱（DOSY）NMR方法来阐明C1576产生的胞外多糖（EpolC1576）与抗生素卡那霉素和头孢地嗪之间的相互作用。本文介绍的NMR策略能够在原子水平上广泛表征EpolC1576参与顽固性现象背后的机制，顽固性现象即生物膜中的细菌在抗生素存在下存活的能力。我们的结果表明，EpolC1576在对卡那霉素和头孢地嗪的顽固性机制中发挥了积极作用，不过是通过两种不同的机制。
