Using a bacterial protein to selectively target bacterial biofilms: Treatment of S. epidermidis biofilms with...

Biofilm-related infections are associated with high mortality and morbidity combined with increased treatment costs. Traditional antibiotics are becoming less effective due to the emergence of drug-resistant bacterial strains. The need to treat biofilms on medical implants is particularly acute, and one persistent challenge is selectively directing nanoparticles to the biofilm site. Here, we present a protein-based functionalization strategy that targets the extracellular matrix of biofilms. The engineered protein combines the Staphylococcus epidermidis autolysin R2ab domain with a gold-binding GB3 domain, directing nanoparticles specifically to bacterial cell wall components (lipoteichoic acid and wall teichoic acid) that are absent in mammalian tissues. This fusion protein is applied to a gold nanoparticle (AuNP) core, along with elastin-like polypeptides (ELPs), which generate a robust photothermal response. The engineered particles exhibit exceptional biocompatibility, including low protein corona formation, minimal macrophage uptake, and hemocompatibility, while maintaining selective biofilm targeting. The photothermal conversion can be modulated by changing the ELP transition temperature, and the functionalized AuNPs strongly interact with biofilms under static and flow conditions without significantly binding to serum-coated surfaces. Near-infrared laser irradiation resulted in a 10,000-fold improvement in killing efficiency compared to untreated controls (p < 0.0001). The targeting strategy utilized here represents a versatile approach to targeting drug-resistant infections and could be readily expanded to other bacterial pathogens and anti-biofilm nanoparticle platforms.