DNA origami nanostructures as a tool for the targeted destruction of bacteria

Abstract

Antibiotic resistance is a growing worldwide human health issue that is now rendering us vulnerable once again to infections that have been treatable for decades. Various approaches have been proposed in an effort to overcome this threat and effectively treat bacterial infections. We use a DNA origami nanostructure, functionalized with aptamers, as a vehicle for delivering the antibacterial peptide lysozyme in a specific and efficient manner, in order to destroy bacterial targets. We test the system against Gram-positive (Bacillus subtilis) and Gram - negative (Escherichia coli) targets. We use direct stochastic optical reconstruction microscopy (dSTORM) and atomic force microscopy (AFM) to characterize the DNA origami nanostructures and structured illumination microscopy (SIM) to assess the binding of origami to the bacteria. We show that treatment with lysozyme-functionalized origami slows bacterial growth more effectively than treatment with free lysozyme. Our study introduces DNA origami as a tool in the fight against antibiotic resistance, and our results demonstrate the specificity and efficiency of the nanostructure as a drug delivery vehicle. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/837252v2_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1d7d8edorg.highwire.dtl.DTLVardef@1e2eb05org.highwire.dtl.DTLVardef@b3c671org.highwire.dtl.DTLVardef@a93a9e_HPS_FORMAT_FIGEXP M_FIG C_FIG