(183aq) High-Throughput Screening of Bacterial Ghost–GPCR Interactions for Targeted Drug Delivery

This project explores the use of Escherichia coli bacterial ghosts—non-living cells with intact membranes but devoid of internal contents—as targeted drug delivery vehicles. E. coli naturally displays surface components capable of interacting with G-protein coupled receptors (GPCRs) on human cells, a superfamily of membrane proteins commonly overexpressed in disease states such as cancer and chronic inflammation. These bacteria–GPCR interactions can mediate adherence, internalization, and modulation of immune responses.

To investigate and harness these interactions, we developed a platform that combines chemically produced bacterial ghosts with high-throughput screening (HTS) against hundreds of human GPCRs. Bacterial ghosts were generated from two commensal E. coli strains and a probiotic strain using a mild chemical lysis method, maintaining membrane integrity while removing intracellular contents. Successful ghost formation was confirmed via DNA release assays and scanning electron microscopy.

HTS was used to identify both adherence interactions and agonist activity, enabling detection of potential targeting mechanisms as well as off-target effects. Screening revealed reproducible activation of signaling with several GPCRs, including known bacteria-host pathways and previously uncharacterized interactions. This is the first demonstration of high-throughput screening of whole bacterial interactions across a broad panel of human GPCRs. Future work will focus on identifying downstream signaling pathways and conducting drug loading and release studies.

This platform provides a scalable and systematic approach to map bacterial–GPCR interactions and evaluate bacterial ghosts as smart delivery vehicles. By leveraging native bacterial surface properties, this work opens new avenues for precise, receptor-guided drug delivery.