UPEC establishes intracellular bacterial communities and persister-like cells in prostate organoid cells

Introduction:

Invasion into the host cell is one of the main pathogenic mechanisms of uropathogenic Escherichia coli (UPEC), enabling them to evade clearance by immune cells and antibiotic treatment. UPEC has developed two ways of surviving within the urothelium: I) by rapidly replicating inside the cell, forming the so-called intracellular bacterial communities—highly tolerant to antibiotics, and II) by remaining quiescent within the cell until conditions become more suitable for intracellular growth. These two mechanisms are essential for UPEC pathogenesis and are directly linked to its ability to induce recurrent infections in the bladder. During a urinary tract infection, UPEC can also infect the prostate; however, whether the bacterium invades these cells and replicates within is not clear so far.

Goals:

To unravel the pathogenesis mechanisms employed by UPEC to invade prostate cells. Through this exploration, we aim to identify previously undiscovered host factors that play a pivotal role in regulating these infections.

Material & Methods:

To study UPEC pathogenesis in a physiological way, we have developed an organoid-based model of the prostate epithelium. We use this model in conjunction with in vitro infection assays (e.g., gentamicin protection assays, immunofluorescence, ligand-capture assays).

Results:

Here, we demonstrate that UPEC can invade prostate organoid cells, and this invasion is dependent on the bacterial adhesin FimH. FimH interacts with different membrane structures than those observed in bladder cells. Additionally, we observe intracellular bacterial communities in these primary prostate cells, as well as solitary bacteria that can survive intracellularly for at least 7 days, similar to what is observed in the bladder epithelium.

Summary:

Overall, we have developed a model that accurately recapitulates the cell structure and composition of the prostate epithelium. Using this model, we are elucidating the tissue-specific mechanisms by which UPEC causes infection of the prostate, holding exciting potential to deepen our understanding of urogenital diseases.