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Identification of potential antimicrobial targets of Pseudomonas aeruginosa biofilms through a novel screening approach

Identification of potential antimicrobial targets of Pseudomonas aeruginosa biofilms through a novel screening approach
Identification of potential antimicrobial targets of Pseudomonas aeruginosa biofilms through a novel screening approach
Pseudomonas aeruginosa is an opportunistic pathogen of considerable medical importance, owing to its pronounced antibiotic tolerance and association with cystic fibrosis and other life-threatening diseases. The aim of this study was to highlight the genes responsible for P. aeruginosa biofilm tolerance to antibiotics and thereby identify potential new targets for the development of drugs against biofilm-related infections. By developing a novel screening approach and utilizing a public P. aeruginosa transposon insertion library, several biofilm-relevant genes were identified. The Pf phage gene (PA0720) and flagellin gene (fliC) conferred biofilm-specific tolerance to gentamicin. Compared with the reference biofilms, the biofilms formed by PA0720 and fliC mutants were completely eliminated with a 4-fold-lower gentamicin concentration. Furthermore, the mreC, pprB, coxC, and PA3785 genes were demonstrated to play major roles in enhancing biofilm tolerance to gentamicin. The analysis of biofilm-relevant genes performed in this study provides important novel insights into the understanding of P. aeruginosa antibiotic tolerance, which will facilitate the detection of antibiotic resistance and the development of antibiofilm strategies against P. aeruginosa.
FliC, PA0720, PA3785, biofilm formation, biofilm tolerance
2165-0497
Valentin, Jules D.P.
63941168-7e62-40a5-8ec8-c2053974ea12
Altenried, Stefanie
80cf5311-3d82-4b9e-855d-727e08fc2ad4
Varadarajan, Adithi R.
ff277cc5-a4fc-46cd-9410-fda3a909b017
Ahrens, Christian H.
70789dbf-86c6-4725-beca-8dfa4b4e1323
Schreiber, Frank
996cc9b1-c439-4fae-8a46-43b94608d034
Webb, Jeremy S.
ec0a5c4e-86cc-4ae9-b390-7298f5d65f8d
van der Mei, Henny C.
41a13fec-7b1c-41ce-b765-a53e30030662
Ren, Qun
fdc42b84-e0e0-4626-b7dd-0bd1d25619bf
Valentin, Jules D.P.
63941168-7e62-40a5-8ec8-c2053974ea12
Altenried, Stefanie
80cf5311-3d82-4b9e-855d-727e08fc2ad4
Varadarajan, Adithi R.
ff277cc5-a4fc-46cd-9410-fda3a909b017
Ahrens, Christian H.
70789dbf-86c6-4725-beca-8dfa4b4e1323
Schreiber, Frank
996cc9b1-c439-4fae-8a46-43b94608d034
Webb, Jeremy S.
ec0a5c4e-86cc-4ae9-b390-7298f5d65f8d
van der Mei, Henny C.
41a13fec-7b1c-41ce-b765-a53e30030662
Ren, Qun
fdc42b84-e0e0-4626-b7dd-0bd1d25619bf

Valentin, Jules D.P., Altenried, Stefanie, Varadarajan, Adithi R., Ahrens, Christian H., Schreiber, Frank, Webb, Jeremy S., van der Mei, Henny C. and Ren, Qun (2023) Identification of potential antimicrobial targets of Pseudomonas aeruginosa biofilms through a novel screening approach. Microbiology Spectrum, 11 (2), [e03099-22]. (doi:10.1128/spectrum.03099-22).

Record type: Article

Abstract

Pseudomonas aeruginosa is an opportunistic pathogen of considerable medical importance, owing to its pronounced antibiotic tolerance and association with cystic fibrosis and other life-threatening diseases. The aim of this study was to highlight the genes responsible for P. aeruginosa biofilm tolerance to antibiotics and thereby identify potential new targets for the development of drugs against biofilm-related infections. By developing a novel screening approach and utilizing a public P. aeruginosa transposon insertion library, several biofilm-relevant genes were identified. The Pf phage gene (PA0720) and flagellin gene (fliC) conferred biofilm-specific tolerance to gentamicin. Compared with the reference biofilms, the biofilms formed by PA0720 and fliC mutants were completely eliminated with a 4-fold-lower gentamicin concentration. Furthermore, the mreC, pprB, coxC, and PA3785 genes were demonstrated to play major roles in enhancing biofilm tolerance to gentamicin. The analysis of biofilm-relevant genes performed in this study provides important novel insights into the understanding of P. aeruginosa antibiotic tolerance, which will facilitate the detection of antibiotic resistance and the development of antibiofilm strategies against P. aeruginosa.

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Accepted/In Press date: 15 January 2023
e-pub ahead of print date: 13 February 2023
Published date: 1 April 2023
Keywords: FliC, PA0720, PA3785, biofilm formation, biofilm tolerance

Identifiers

Local EPrints ID: 476685
URI: http://eprints.soton.ac.uk/id/eprint/476685
ISSN: 2165-0497
PURE UUID: 0fb4f73e-b4c5-4d1c-b14a-c367d7c87bf3
ORCID for Jeremy S. Webb: ORCID iD orcid.org/0000-0003-2068-8589

Catalogue record

Date deposited: 11 May 2023 16:40
Last modified: 20 May 2023 01:38

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Contributors

Author: Jules D.P. Valentin
Author: Stefanie Altenried
Author: Adithi R. Varadarajan
Author: Christian H. Ahrens
Author: Frank Schreiber
Author: Jeremy S. Webb ORCID iD
Author: Henny C. van der Mei
Author: Qun Ren

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