Guiding antibiotics towards their target using bacteriophage proteins

Abstract

Abstract Novel therapeutic strategies against difficult-to-treat bacterial infections are desperately needed, and the faster and cheaper way to get them might be by repurposing existing antibiotics. Nanodelivery systems enhance the efficacy of antibiotics by guiding them to their targets, increasing the local concentration at the site of infection. While recently described nanodelivery systems are promising, they are generally not easy to adapt to different targets, and lack biocompatibility or specificity. Here, nanodelivery systems are created that source their targeting proteins from bacteriophages. Bacteriophage receptor-binding proteins and cell-wall binding domains were conjugated to nanoparticles, for the targeted delivery of rifampicin against bacterial pathogens. They showed excellent specificity against their targets, and accumulated at the site of infection to deliver their antibiotic payload. Moreover, the nanodelivery systems suppressed pathogen infections more effectively than higher doses of free antibiotic. This study demonstrates that bacteriophage sourced targeting proteins are promising candidates to guide nanodelivery systems. Their specificity, availability, and biocompatibility make them great options to guide the antibiotic nanodelivery systems that are desperately needed to combat difficult-to-treat infections.