Biohybrid Microswimmers Against Bacterial Infections

Abstract

Biohybrid microswimmers exploit the natural abilities of motile microorganisms e.g. in releasing cargo on-demand with high spatial and temporal control. However, using such engineered swarms to deliver antibiotics addressing bacterial infections has not yet been realized. In the present study, a design strategy for biohybrid microswimmers is reported, which features the covalent attachment of antibiotics to the motile green algae Chlamydomonas reinhardtii via a photo-cleavable linker. The surface engineering of the algae does not rely on genetic manipulations, proceeds with high efficiency, does not impair the viability or phototactic ability of microalgae, and allows for caging of the antibiotic on the surface for subsequent release via external stimuli. Two different antibiotic classes have been separately utilized, which result in activity against both gram-positive and gram-negative strains. Guiding the biohybrid microswimmers by an external beacon, and on-demand delivery of the drugs by light with high spatial and temporal control, allowed for strong inhibition of bacterial growth in vivo. This efficient strategy could potentially allow for the selective treatment of bacterial infections by engineered algal microrobots with high precision in space and time. Overall, this work presents an operationally simple production of biohybrid microswimmers loaded with antibiotic cargo to combat bacterial infections precisely delivered in three-dimensional space.