Uropathogenic Escherichia coli invade luminal prostate cells via FimH-PPAP receptor binding

Area of Science:

• Urology
• Microbiology
• Cell Biology

Background:

• Bacterial prostatitis, often caused by UPEC, is a common and recurring infection in men.
• The molecular mechanisms of prostatitis are not fully understood, partly due to limited in vitro models.

Purpose of the Study:

• To develop and validate a novel 2D mouse stem cell-derived prostate epithelial organoid model for studying bacterial prostatitis.
• To investigate the role of UPEC adhesin FimH in the pathogenesis of prostatitis.

Main Methods:

• Development of a 2D prostate epithelial organoid model.
• Transcriptomic analysis for model validation.
• UPEC infection assays with wild-type and FimH mutant strains.
• Biochemical assays (immunoprecipitation, mass spectrometry) to identify host-pathogen interactions.
• Host gene knockout experiments and ex vivo human prostate tissue validation.

Main Results:

• The organoid model recapitulates key features of prostate epithelial differentiation and UPEC infection.
• UPEC preferentially infects and replicates within luminal prostate cells.
• FimH-mediated binding to prostatic acid phosphatase (PPAP) is crucial for UPEC invasion.
• D-Mannose competitively inhibits FimH-PPAP interactions, reducing bacterial invasion.

Conclusions:

• The developed organoid model is a valuable tool for studying prostatitis.
• FimH-PPAP interaction is a key mechanism for UPEC invasion in the prostate.
• Targeting FimH presents a potential therapeutic strategy for bacterial prostatitis.