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Significance Pseudomonas aeruginosa is one of the leading causes of hospital-acquired infections worldwide primarily due to its ability to develop antibiotic-resistant biofilms. This report describes a mechanism whereby human airway epithelial cells (AECs) increase the ability of antibiotics to killP. aeruginosa and reduce the formation of drug-resistant biofilms. We demonstrate that human AECs secrete extracellular vesicles containing the microRNA let-7b-5p, that the vesicles deliver let-7b-5p toP. aeruginosa , and that let-7b-5p decreases biofilm formation and increases the ability of beta-lactam antibiotics to reduce biofilm formation by down-regulating key antibiotic-resistance and biofilm genes. A combination of let-7b, which is in clinical trials as an anti-inflammatory agent, and beta-lactam antibiotics may help combat antibiotic-resistantP. aeruginosa infections.

Let-7b-5p in vesicles secreted by human airway cells reduces biofilm formation and increases antibiotic sensitivity of P. aeruginosa