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DNA Origami as a Tool in the Targeted Destruction of Bacteria

Mela I, Endo M, Sugiyama H, Henderson R, Kaminski CF. "DNA origami as a tool in the targeted destruction of bacteria." Biophysical Journal (2019), 116(3):324a. DOI |pdfsummary 



Antibiotic resistance is a growing worldwide human health issue. It is now
threatening to render us vulnerable once again to infections that have been
treatable for decades. Various approaches have been proposed in the effort
to overcome this threat and effectively treat bacterial infections. We explore
the possibility of creating and using DNA origami nanostructures as a
vehicle for delivering functional molecules in a specific and efficient
manner, in order to destroy bacterial targets. In the past few years, DNA
origami has been used to successfully target eukaryotic cancer cells, with
impressive results. However, there are no reports of the use of DNA origami
to specifically target bacterial cells. We have created a DNA origami tile
with five ‘‘wells’’ that can carry up to 10 molecules of antibacterial lysozyme. The origami tile has been modified to carry four aptamers that are specific to Escherichia coli bacteria and enable anchoring of tiles onto a
bacterium. Each origami tile measures approximately 100 x 100 nm, allowing for multiple tiles to attach to any bacterium. We use direct stochastic optical reconstruction microscopy (dSTORM) to assess the efficiency of
targeting the tile to the bacteria and we show that treatment with
lysozyme-functionalised tiles slows bacterial growth more effectively than
treatment with free lysozyme. We also assess the mechanical properties of
the origami-treated bacteria with atomic force microscopy. 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