Human Lung Microtissues to Study Bacterial Infection and Treatment

The discovery of novel antibiotic compounds has been stagnated for many years. As this is in part due to the nature of the currently used in vitro and in vivo models, there is an urgent need for experimental models that faithfully recapitulate the physiology of human tissue, have the experimental power to investigate the infection process with high temporal and spatial resolution and accommodate better precision in the selection for antimicrobial efficacy in patients.
We established an in vivo-like lung infection model from human stem cells, with air-liquid interface in a Transwell. Using this fully differentiated and pseudo-stratified tissue model, we visualized and quantified P. aeruginosa lung infection providing a detailed mechanistic frame for how human pathogens overcome the mucus barrier and rapidly spread on mucosal tissue to effectively breach the barrier function of the lung epithelium. We currently aim to evaluate and establish the Transwell lung model as a novel and highly predictive in vitro tool to assess pharmacokinetics and pharmacodynamics of antibiotics, thereby studying drug response in a human-like environment and facilitating the discovery of novel antimicrobial compounds with high translational potential to clinical efficacy.

Host: Andreas Peschel

Lecture hall 3M07, GUZ