Two articles use organoids + chips to reveal how bacteria invade the bladder

The "community" breaks down repeatedly, and the bacteria re-enter the neighboring cells, eventually killing the so-called "umbrella cells" in the outermost layer of the bladder epithelium

Kunal Sharma, the lead author of the two studies, said: “It is difficult to capture the dynamics of infection from the static imaging of tissue explants at consecutive time points

To solve this problem, the group of Professor John D McKinney of the EPFL School of Life Sciences has developed two complementary bladder models to study UTIs in a more controlled manner

The second model is a bladder on a chip, including physiological stimuli, such as the mechanical effects of bladder filling and urination, and the interface with the vasculature to study the migration of immune cells to the site of infection

Sharma said: "By implanting fluorescent tags in the cell membrane of mice to produce organoids, we can use live cell confocal imaging in EPFL's bioimaging and optical core facilities to identify specific bacteria in organoids with high spatial resolution.

Combined with the volumetric electron microscope performed by the EPFL biological electron microscope equipment, the researchers found that independent of the formation of intracellular bacterial communities, isolated bacteria quickly invade the deep layer of the bladder, where they are protected by antibiotics and host immune cells

In the bladder model on a complementary chip, the researchers observed the growth dynamics of the bacterial community in the cell over time

This study focuses on the role of neutrophil recruitment in the infection response, revealing that neutrophils cannot eliminate the intracellular bacterial community

"Micro-physiological models bridge the gap between simple cell culture systems and animal models," said Vivek V.

Kunal Sharma, Neeraj Dhar, Vivek V Thacker, Thomas M Simonet, Francois Signorino-Gelo, Graham William Knott, John D McKinney.