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Pseudomonas aeruginosa detachment from surfaces via a self-made small molecule.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2021 Jan-Jun; Vol. 296, pp. 100279. Date of Electronic Publication: 2021 Jan 12. - Publication Year :
- 2021
-
Abstract
- Pseudomonas aeruginosa is a significant threat in both healthcare and industrial biofouling. Surface attachment of P. aeruginosa is particularly problematic as surface association induces virulence and is necessary for the ensuing process of biofilm formation, which hampers antibiotic treatments. Previous efforts have searched for dispersal agents of mature biofilm collectives, but there are no known factors that specifically disperse individual surface-attached P. aeruginosa. In this study, we develop a quantitative single-cell surface-dispersal assay and use it to show that P. aeruginosa itself produces factors that can stimulate its dispersal. Through bioactivity-guided fractionation, mass spectrometry, and nuclear magnetic resonance, we elucidated the structure of one such factor, 2-methyl-4-hydroxyquinoline (MHQ). MHQ is an alkyl quinolone with a previously unknown activity and is synthesized by the PqsABC enzymes. Pure MHQ is sufficient to disperse P. aeruginosa, but the dispersal activity of natural P. aeruginosa conditioned media requires additional factors. Whereas other alkyl quinolones have been shown to act as antibiotics or membrane depolarizers, MHQ lacks these activities and known antibiotics do not induce dispersal. In contrast, we show that MHQ inhibits the activity of Type IV Pili (TFP) and that TFP targeting can explain its dispersal activity. Our work thus identifies single-cell surface dispersal as a new activity of P. aeruginosa-produced small molecules, characterizes MHQ as a promising dispersal agent, and establishes TFP inhibition as a viable mechanism for P. aeruginosa dispersal.<br />Competing Interests: Conflict of interest A provisional patent describing MHQ as a potential therapeutic in surface dispersal has been filed.<br /> (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Aniline Compounds chemistry
Fimbriae, Bacterial drug effects
Fimbriae, Bacterial genetics
Gene Expression Regulation, Bacterial
Humans
Pseudomonas Infections microbiology
Pseudomonas Infections pathology
Pseudomonas aeruginosa pathogenicity
Quinolones pharmacology
Single-Cell Analysis
Virulence drug effects
Biofilms drug effects
Hydroxyquinolines pharmacology
Pseudomonas Infections drug therapy
Pseudomonas aeruginosa genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 296
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 33450229
- Full Text :
- https://doi.org/10.1016/j.jbc.2021.100279