1, University of California, Riverside, Riverside, California, United States
Antibiotic resistant bacteria have increasingly become an issue in both the environment and in the human body. Photothermal lysis, using the plasmonic properties of metal nanoparticles (NPs), has been shown to be effective against bacteria, regardless of their drug resistance. Typically, these particles need to be functionalized with specific bacteria-targeting molecules and the particle geometries tailored to the desired spectral absorption range. Viruses provide an alternative approach to the synthesis of these bacteria targeting metal nanoparticles. Through genetic modification, a virus can be programmed to simultaneously serve as a scaffold for metal nanostructure assembly and have an affinity for a specific bacterial host. In this work, we used a gold-binding M13 bacteriophage to create a photothermal bactericide for e coli. The filamentous virus was modified to display an 8-mer peptide with gold affinity on the major coat protein, while the unmodified minor coat protein was used to specifically target e coli F pili. To create a nanoshell template, the virus underwent a simple chloroform treatment causing it to contract from its filamentous form to its spheroidal form. Two different types of gold nanoshells were formed: one by binding gold nanoparticles to the spheroid surface for visible light absorption and the other by synthesizing a gold shell on the spheroid surface for near infrared absorption. Transmission electron microscopy and spectrophotometry were used to evaluate shell morphology and optical absorption, respectively. Nanoshell photothermal activity was quantified under either green (532 nm) or near infrared (785 nm) laser illumination. Significant antibacterial activity was measured via colony titer count. The use of gold/M13 bacteriophage nanoshells as a photothermal bactericide was demonstrated in this study by utilizing the innate affinity of the unmodified M13 minor coat protein for e coli f pili. However, this potentially powerful approach can be generalized to target a variety of bacteria through the incorporation of affinity peptide fusions.