气候变化领域集成服务门户(CCPortal): Let-7b-5p in vesicles secreted by human airway cells reduces biofilm formation and increases antibiotic sensitivity of P. aeruginosa

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DOI	10.1073/pnas.2105370118
	Let-7b-5p in vesicles secreted by human airway cells reduces biofilm formation and increases antibiotic sensitivity of P. aeruginosa
	Koeppen K.; Nymon A.; Barnaby R.; Bashor L.; Li Z.; Hampton T.H.; Liefeld A.E.; Kolling F.W.; LaCroix I.S.; Gerber S.A.; Hogan D.A.; Kasetty S.; Nadell C.D.; Stanton B.A.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:28
英文摘要	Pseudomonas aeruginosa is an opportunistic pathogen that forms antibiotic-resistant biofilms, which facilitate chronic infections in immunocompromised hosts. We have previously shown that P. aeruginosa secretes outer-membrane vesicles that deliver a small RNA to human airway epithelial cells (AECs), in which it suppresses the innate immune response. Here, we demonstrate that interdomain communication through small RNA–containing membrane vesicles is bidirectional and that microRNAs (miRNAs) in extracellular vesicles (EVs) secreted by human AECs regulate protein expression, antibiotic sensitivity, and biofilm formation by P. aeruginosa. Specifically, human EVs deliver miRNA let-7b-5p to P. aeruginosa, which systematically decreases the abundance of proteins essential for biofilm formation, including PpkA and ClpV1-3, and increases the ability of beta-lactam antibiotics to reduce biofilm formation by targeting the beta-lactamase AmpC. Let-7b-5p is bioinformatically predicted to target not only PpkA, ClpV1, and AmpC in P. aeruginosa but also the corresponding orthologs in Burkholderia cenocepacia, another notorious opportunistic lung pathogen, suggesting that the ability of let-7b-5p to reduce biofilm formation and increase beta-lactam sensitivity is not limited to P. aeruginosa. Here, we provide direct evidence for transfer of miRNAs in EVs secreted by eukaryotic cells to a prokaryote, resulting in subsequent phenotypic alterations in the prokaryote as a result of this interdomain communication. Since let-7–family miRNAs are in clinical trials to reduce inflammation and because chronic P. aeruginosa lung infections are associated with a hyperinflammatory state, treatment with let-7b-5p and a beta-lactam antibiotic in nanoparticles or EVs may benefit patients with antibiotic-resistant P. aeruginosa infections. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Airway epithelial cells; Exosomes; Extracellular vesicles; Host–pathogen communication; RNAi
语种	英语
scopus关键词	antagomir; antiinfective agent; aztreonam; beta lactam; microRNA; mirnlet7 microRNA, human; biofilm; drug effect; exosome; gene expression regulation; genetics; growth, development and aging; human; isolation and purification; metabolism; physiology; plankton; Pseudomonas aeruginosa; Antagomirs; Anti-Bacterial Agents; Aztreonam; beta-Lactams; Biofilms; Extracellular Vesicles; Gene Expression Regulation, Bacterial; Humans; MicroRNAs; Plankton; Pseudomonas aeruginosa
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251133
作者单位	Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, United States; Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, NH 03756, United States; Department of Biological Sciences, Dartmouth College, Hanover, NH 03755, United States
推荐引用方式 GB/T 7714	Koeppen K.,Nymon A.,Barnaby R.,et al. Let-7b-5p in vesicles secreted by human airway cells reduces biofilm formation and increases antibiotic sensitivity of P. aeruginosa[J],2021,118(28).
APA	Koeppen K..,Nymon A..,Barnaby R..,Bashor L..,Li Z..,...&Stanton B.A..(2021).Let-7b-5p in vesicles secreted by human airway cells reduces biofilm formation and increases antibiotic sensitivity of P. aeruginosa.Proceedings of the National Academy of Sciences of the United States of America,118(28).
MLA	Koeppen K.,et al."Let-7b-5p in vesicles secreted by human airway cells reduces biofilm formation and increases antibiotic sensitivity of P. aeruginosa".Proceedings of the National Academy of Sciences of the United States of America 118.28(2021).