Biohybrid microswimmers against bacterial infections

Abstract

Biohybrid microswimmers exploit the natural abilities of motile microorganisms e.g. in releasing cargo on-demand. However, using such engineered swarms to release antibiotics addressing bacterial infections has not yet been realized. Herein, a design strategy for biohybrid microswimmers is reported, which features the covalent attachment of antibiotics with a photo-cleavable linker to the algae Chlamydomonas reinhardtii via two synthetic steps. This surface engineering does not rely on genetic manipulations, proceeds with high efficiency, and retains the viability or phototaxis of microalgae. Two different antibiotics 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. This efficient strategy could potentially allow for the selective treatment of bacterial infections by engineered algal microrobots with high precision in space and time. STATEMENT OF SIGNIFICANCE: Biological swimmers with innate sensing and actuation capabilities and integrated components have been widely investigated to create autonomous microsystems. The use of natural swimmers as cargo delivery systems presents an alternative strategy to transport therapeutics to the required locations with the difficult access by traditional strategies. Although the transfer of various therapeutic cargo has shown promising results, the utilization of microswimmers for the delivery of antimicrobials was barely covered. Therefore, we present biohybrid microalga-powered swimmers designed and engineered to carry antibiotic cargo against both Gram-positive and Gram-negative bacteria. Guided by an external beacon, these microhybrids deliver the antibiotic payload to the site of bacterial infection, with high spatial and temporal precision, released on-demand by an external trigger to inhibit bacterial growth.

Keywords: Antibacterial agents; Biohybrids; Chlamydomonas reinhardtii; Drug delivery; Microalgae; Microswimmers; Phototaxis.