Dosage‐Dependent Antimicrobial Activity of DNA‐Histone Microwebs Against Staphylococcus Aureus

Abstract

Neutrophil extracellular traps (NETs) are antimicrobial cobweb‐structured materials produced by immune cells for clearance of pathogens in the body, but are paradoxically associated with biofilm formation and exacerbated lung infections. To provide a better materials perspective on the pleiotropic roles played by NETs at diverse compositions/concentrations, a NETs‐like material (called “microwebs”, abbreviated as μwebs) is synthesized for decoding the antimicrobial activity of NETs against Staphylococcus aureus in infection‐relevant conditions. It is shown that μwebs composed of low‐to‐intermediate concentrations of DNA‐histone complexes successfully trap and inhibit S. aureus growth and biofilm formation. However, with growing concentrations and histone proportions, the resulting microwebs appear gel‐like structures accompanied by reduced antimicrobial activity that can even promote the formation of S. aureus biofilms. The simplified model of NETs provides materials‐based evidence on NETs‐relevant pathology in the development of biofilms.“Microwebs”, a web‐like DNA structure mimicking the neutrophil extracellular traps (NETs) shows antimicrobial activity against Staphylococcus aureus at physiological conditions, but it paradoxically induces biofilm formation at higher concentrations. This paradigm can be explained under the framework of electrostatic interactions between DNA, histone, and bacterial cell walls, which provides a materials‐based insight for understanding the NETs‐relevant pathology in the biofilm disease.