Enhanced bacterial killing by vancomycin in staphylococcal biofilms disrupted by novel, DMMA-modified carbon dots depends on EPS production
Yanyan Wu, Henny C. van der Mei, Henk J. Busscher, Yijin Ren
Abstract
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 (CDMMA-dots). CDMMA-dots, like unmodified C-dots without DMMA, were little bactericidal. However, CDMMA-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 CDMMA-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.