Antibiotic Efficacy and Enterobacterial Resistance Spread in Infected Human Tissue Resolved by Organoid Modelling

Antibiotics are crucial for modern medicine, but resistance spread threatens their use and urges the need for intensified research.

Studies of bacterium - antibiotic interactions and bacterial resistance are typically conducted on simple agar plates or in liquid broth. While useful, such analyses fail to recapitulate the conditions in infected host tissue.

This hampers our understanding of antibiotic action and the basis for treatment success or failure during a “real infection”. Organoids, cultured miniature organs, have emerged as powerful tools to study human disease.

Here, I describe an organoid-based approach to reconstruct enterobacterium-infected gut tissue ex vivo and assess antibiotic efficacy and bacterial resistance spread in a relevant infection context.

We will trace in real time how clinically used antibiotics act on prominent enterobacteria when lodged within colonized tissue compartments.

Live imaging will be combined with cutting edge tools for bacterial genetics and sensitive mass spectrometry to measure antibiotic concentrations at discrete sites.

The work aims to i) uncover the basis for antibiotic efficacy/non-efficacy in infected tissue, ii) pinpoint particular antibiotic-vulnerable stages of bacterial infection cycles, and iii) explain how the tissue context and host defenses affect spread of resistance elements during an infection. This will provide a powerful framework to predict the outcome of current and emerging antibiotic therapies in vivo.