Enhanced bacterial killing by vancomycin in staphylococcal biofilms disrupted by novel, DMMA-modified carbon dots depends on EPS production

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.