University of Groningen and University Medical Center of Groningen Department of Orthodontics, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
University of Groningen and University Medical Center Groningen Department of Biomedical Engineering, Antonius Deusinglaan 1, 9713 AV Groningen, the Netherlands.
Colloids Surf B Biointerfaces. 2020 Sep;193:111114. doi: 10.1016/j.colsurfb.2020.111114. Epub 2020 May 12.
Alternatives for less and less effective antibiotic treatment of bacterial infections, are amongst others based on nanotechnological innovations, like carbon-dots. However, with a focus on chemistry, important characteristics of bacterial strains, like (in-)ability to produce extracellular-polymeric-substances (EPS) are often neglected. EPS is the glue that certain bacterial strains produce to keep a biofilm together. Here we report on synthesis of novel, pH-responsive, 2,3-dimethylmaleic-anhydride modified carbon-dots (C-dots). C-dots, like unmodified C-dots without DMMA, were little bactericidal. However, C-dots reduced volumetric-bacterial-density within the acidic-environment of a biofilm for a non-EPS-producing Staphylococcus epidermidis strain, indicative for a more open structure. Such a structural disruption was not observed for an EPS-producing strain. Disrupted biofilms of the non-EPS-producing strain pre-exposed to C-dots at pH 5.0, were more amenable to vancomycin penetration and killing of their inhabitants than biofilms of EPS-producing-staphylococci. Herewith, we describe a new role of carbon-dots as synthetic disruptants of biofilm structure. It is a partial success story, identifying the challenge of making carbon-dots that act as a universal disruptant for biofilms of strains with different microbiological characteristics, most notably the ability to produce or not-produce EPS. Such carbon-dots, will enable more effective clinical treatment of bacterial infections combined with current antibiotics.
替代抗生素治疗细菌感染的方法越来越少，其中一些方法基于纳米技术创新，如碳点。然而，由于侧重于化学，某些细菌菌株的重要特性（如产生细胞外聚合物物质（EPS）的能力）往往被忽视。EPS 是某些细菌菌株产生的胶水，用于将生物膜保持在一起。在这里，我们报告了新型 pH 响应的 2,3-二甲基马来酸酐修饰的碳点（C 点）的合成。C 点与未用 DMMA 修饰的 C 点一样，杀菌作用很小。然而，对于不产生 EPS 的表皮葡萄球菌菌株，C 点在生物膜的酸性环境中减少了体积细菌密度，表明结构更加开放。对于产生 EPS 的菌株，未观察到这种结构破坏。在 pH 值为 5.0 时预先用 C 点暴露的非 EPS 产生菌株的生物膜中，比产生 EPS 的葡萄球菌生物膜更容易渗透万古霉素并杀死其居民。由此，我们描述了碳点作为生物膜结构合成破坏剂的新作用。这是一个部分成功的故事，确定了制造碳点的挑战，即作为具有不同微生物学特性的菌株的生物膜的通用破坏剂，尤其是产生或不产生 EPS 的能力。这种碳点将使结合当前抗生素的细菌感染的临床治疗更加有效。
