{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:32:01Z","timestamp":1791221521053,"version":"4.1.0"},"reference-count":23,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T00:00:00Z","timestamp":1766620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian University Ministry","award":["PE13_INFACT_PNRR-U.A. 14.01"],"award-info":[{"award-number":["PE13_INFACT_PNRR-U.A. 14.01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013Vav3\u2013Fn axis, reducing bacterial attachment. This host-directed approach represents a promising strategy to prevent chronic infections in CF without promoting antibiotic resistance.<\/jats:p>","DOI":"10.3390\/ijms27010232","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:50:21Z","timestamp":1766710221000},"page":"232","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["HuR-Targeted Small Molecules Reduce Pseudomonas aeruginosa Adhesion in Cystic Fibrosis Airway Epithelial Cells"],"prefix":"10.3390","volume":"27","author":[{"given":"Roberta","family":"Listro","sequence":"first","affiliation":[{"name":"Department of Drug Science, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3339-3952","authenticated-orcid":false,"given":"Angelica","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Pavia, Via Taramelli 3B, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1008-5736","authenticated-orcid":false,"given":"Giacomo","family":"Rossino","sequence":"additional","affiliation":[{"name":"Department of Drug Science, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0382-7479","authenticated-orcid":false,"given":"Pasquale","family":"Linciano","sequence":"additional","affiliation":[{"name":"Department of Drug Science, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7069-8155","authenticated-orcid":false,"given":"Giampiero","family":"Pietrocola","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Pavia, Via Taramelli 3B, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2954-7558","authenticated-orcid":false,"given":"Simona","family":"Collina","sequence":"additional","affiliation":[{"name":"Department of Drug Science, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,25]]},"reference":[{"key":"ref_1","unstructured":"Antimicrobial Resistance Collaborators (2022). 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