Work

HuR-Targeted Small Molecules Reduce Pseudomonas aeruginosa Adhesion in Cystic Fibrosis Airway Epithelial Cells

Year: 2025

Type: article

Abstract: Antibiotic-resistant infections remain a major challenge in cystic fibrosis (CF), where chronic Pseudomonas aeruginosa colonization drives lung infection. The overexpression of adhesion-related proteins and extracellular matrix components, including fibronectin (Fn), facilitates bacterial colonization. Recent evidence identifies the RNA-binding protein Human Antigen R (HuR) as a key regulator of this process, as it stabilizes Vav3 mRNA, promoting Fn deposition and the formation of bacterial docking platforms. Here, we report the synthesis, optimization, and functional evaluation of the HuR-targeted small-molecule (2S,3S)-BOPC1. Functional assays in CF human airway epithelial cells demonstrated that (2S,3S)-BOPC1 significantly reduced P. aeruginosa adhesion in a dose-dependent manner without detectable cytotoxic effects. These findings provide the first evidence that targeting HuR can disrupt the HuR–Vav3–Fn axis, reducing bacterial attachment. This host-directed approach represents a promising strategy to prevent chronic infections in CF without promoting antibiotic resistance.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms27010232

Authors: Roberta Listro, Angelica Pellegrini, Giacomo Rossino, Pasquale Linciano, Giampiero Pietrocola, Simona Collina

Institution: University of Pavia

Language: English

Topic: Bacterial biofilms and quorum sensing

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499