Bacterial Breaching of a Physiologically Arranged Intestinal Epithelial Barrier

Gut bacterial infections – caused by e.g. Salmonella, Shigella and Campylobacter species – impose a major global health burden. The impact is predicted to increase further, due to the rapid rise in antibiotic resistant isolates.

These pathogens use virulence factors to target, bind and invade into the intestinal epithelial cell barrier that lines the gut lumen.

Breaching of this key barrier elicits gut inflammation and can cause the potentially lethal spread of bacteria to the blood and sterile organs.

An accurate understanding of pathogen - epithelium interplay is crucial to explain and best treat bacterial infectious disease. However, current knowledge stems largely from experiments in simple tumor cell lines.

It therefore remains poorly understood how the pathogens interact with a physiologically arranged “real” gut epithelium.

Here, we will combine large-scale bacterial genetics and live-cell imaging with advanced organoid models that faithfully capture the features of the intact human gut epithelium.

We will explain how major bacterial pathogens i) search for suitable epithelial invasion sites by flagellar motility, ii) engage with the segment- and cell type-specific apical epithelial surface to invade, and how iii) the epithelium fends for its integrity in response to this onslaught.

The work has potential to uncover the parameters dictating whether or not bacterial attack on the epithelium causes barrier breaching - a decisive event in bacterial infection medicine.