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

Authors: Katja Koeppen, Amanda Nymon, Roxanna Barnaby, Laura Bashor, Zhongyou Li, Thomas H. Hampton, Amanda Liefeld, Fred Kolling, Ian S. LaCroix, Scott A. Gerber, Deborah A. Hogan, Swetha Kasetty, Carey D. Nadell, Bruce A. Stanton - Proceedings of the National Academy of Sciences, PNAS 2021 cited by 61

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 kill P. 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 to P. 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-resistant P. aeruginosa infections.