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Environmental factors are vital for bacterial successful colonization. Here, with sputa and bronchoalveolar lavage fluids, we determined that the concentration of airway antimicrobial peptide LL\u201037 and lactate was elevated in BE patients, especially in those infected with <jats:italic>P. aeruginosa<\/jats:italic>. The in vitro antibacterial assay revealed the bactericidal activity of LL\u201037 against the clinical <jats:italic>P. aeruginosa<\/jats:italic> isolates, which were dampened in the acidic condition. <jats:italic>P. aeruginosa<\/jats:italic> production of outer membrane vesicles (OMVs) enhanced in the lactate\u2010adjusted acidic condition. Transcriptomic analysis suggested that OMVs induce the hyperproduction of the chemical compound 2\u2010heptyl\u20104\u2010quinolone (HHQ) in the bacterial population, which was verified by high\u2010performance liquid chromatography. The positively charged HHQ interfered with the binding of LL\u201037 to bacterial cell membrane, potentiating the <jats:italic>P. aeruginosa<\/jats:italic> resistance to LL\u201037. To our knowledge, this is a new resistance mechanism of <jats:italic>P. aeruginosa<\/jats:italic> against antimicrobial peptides and may provide theoretical support for the development of new antibacterial therapies.<\/jats:p>","DOI":"10.1002\/mco2.70084","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T07:26:20Z","timestamp":1738308380000},"source":"Crossref","is-referenced-by-count":7,"title":["Outer membrane vesicle contributes to the <i>Pseudomonas aeruginosa<\/i> resistance to antimicrobial peptides in the acidic airway of bronchiectasis patients"],"prefix":"10.1002","volume":"6","author":[{"given":"Yingzhou","family":"Xie","sequence":"first","affiliation":[{"name":"Shanghai Pulmonary Hospital, Institute of Respiratory Medicine, School of Medicine Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Han","family":"Shi","sequence":"additional","affiliation":[{"name":"Shanghai Pulmonary 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