Cargando…
Halogenated Dihydropyrrol-2-One Molecules Inhibit Pyocyanin Biosynthesis by Blocking the Pseudomonas Quinolone Signaling System
Quorum-sensing (QS) systems of Pseudomonas aeruginosa are involved in the control of biofilm formation and virulence factor production. The current study evaluated the ability of halogenated dihydropyrrol-2-ones (DHP) (Br (4a), Cl (4b), and F (4c)) and a non-halogenated version (4d) to inhibit the Q...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875348/ https://www.ncbi.nlm.nih.gov/pubmed/35208954 http://dx.doi.org/10.3390/molecules27041169 |
_version_ | 1784657891342417920 |
---|---|
author | Das, Theerthankar Sabir, Shekh Chen, Ren Farrell, Jessica Kriel, Frederik H. Whiteley, Gregory S. Glasbey, Trevor O. Manos, Jim Willcox, Mark D. P. Kumar, Naresh |
author_facet | Das, Theerthankar Sabir, Shekh Chen, Ren Farrell, Jessica Kriel, Frederik H. Whiteley, Gregory S. Glasbey, Trevor O. Manos, Jim Willcox, Mark D. P. Kumar, Naresh |
author_sort | Das, Theerthankar |
collection | PubMed |
description | Quorum-sensing (QS) systems of Pseudomonas aeruginosa are involved in the control of biofilm formation and virulence factor production. The current study evaluated the ability of halogenated dihydropyrrol-2-ones (DHP) (Br (4a), Cl (4b), and F (4c)) and a non-halogenated version (4d) to inhibit the QS receptor proteins LasR and PqsR. The DHP molecules exhibited concentration-dependent inhibition of LasR and PqsR receptor proteins. For LasR, all compounds showed similar inhibition levels. However, compound 4a (Br) showed the highest decrease (two-fold) for PqsR, even at the lowest concentration (12.5 µg/mL). Inhibition of QS decreased pyocyanin production amongst P. aeruginosa PAO1, MH602, ATCC 25619, and two clinical isolates (DFU-53 and 364707). In the presence of DHP, P. aeruginosa ATCC 25619 showed the highest decrease in pyocyanin production, whereas clinical isolate DFU-53 showed the lowest decrease. All three halogenated DHPs also reduced biofilm formation by between 31 and 34%. The non-halogenated compound 4d exhibited complete inhibition of LasR and had some inhibition of PqsR, pyocyanin, and biofilm formation, but comparatively less than halogenated DHPs. |
format | Online Article Text |
id | pubmed-8875348 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88753482022-02-26 Halogenated Dihydropyrrol-2-One Molecules Inhibit Pyocyanin Biosynthesis by Blocking the Pseudomonas Quinolone Signaling System Das, Theerthankar Sabir, Shekh Chen, Ren Farrell, Jessica Kriel, Frederik H. Whiteley, Gregory S. Glasbey, Trevor O. Manos, Jim Willcox, Mark D. P. Kumar, Naresh Molecules Article Quorum-sensing (QS) systems of Pseudomonas aeruginosa are involved in the control of biofilm formation and virulence factor production. The current study evaluated the ability of halogenated dihydropyrrol-2-ones (DHP) (Br (4a), Cl (4b), and F (4c)) and a non-halogenated version (4d) to inhibit the QS receptor proteins LasR and PqsR. The DHP molecules exhibited concentration-dependent inhibition of LasR and PqsR receptor proteins. For LasR, all compounds showed similar inhibition levels. However, compound 4a (Br) showed the highest decrease (two-fold) for PqsR, even at the lowest concentration (12.5 µg/mL). Inhibition of QS decreased pyocyanin production amongst P. aeruginosa PAO1, MH602, ATCC 25619, and two clinical isolates (DFU-53 and 364707). In the presence of DHP, P. aeruginosa ATCC 25619 showed the highest decrease in pyocyanin production, whereas clinical isolate DFU-53 showed the lowest decrease. All three halogenated DHPs also reduced biofilm formation by between 31 and 34%. The non-halogenated compound 4d exhibited complete inhibition of LasR and had some inhibition of PqsR, pyocyanin, and biofilm formation, but comparatively less than halogenated DHPs. MDPI 2022-02-09 /pmc/articles/PMC8875348/ /pubmed/35208954 http://dx.doi.org/10.3390/molecules27041169 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Das, Theerthankar Sabir, Shekh Chen, Ren Farrell, Jessica Kriel, Frederik H. Whiteley, Gregory S. Glasbey, Trevor O. Manos, Jim Willcox, Mark D. P. Kumar, Naresh Halogenated Dihydropyrrol-2-One Molecules Inhibit Pyocyanin Biosynthesis by Blocking the Pseudomonas Quinolone Signaling System |
title | Halogenated Dihydropyrrol-2-One Molecules Inhibit Pyocyanin Biosynthesis by Blocking the Pseudomonas Quinolone Signaling System |
title_full | Halogenated Dihydropyrrol-2-One Molecules Inhibit Pyocyanin Biosynthesis by Blocking the Pseudomonas Quinolone Signaling System |
title_fullStr | Halogenated Dihydropyrrol-2-One Molecules Inhibit Pyocyanin Biosynthesis by Blocking the Pseudomonas Quinolone Signaling System |
title_full_unstemmed | Halogenated Dihydropyrrol-2-One Molecules Inhibit Pyocyanin Biosynthesis by Blocking the Pseudomonas Quinolone Signaling System |
title_short | Halogenated Dihydropyrrol-2-One Molecules Inhibit Pyocyanin Biosynthesis by Blocking the Pseudomonas Quinolone Signaling System |
title_sort | halogenated dihydropyrrol-2-one molecules inhibit pyocyanin biosynthesis by blocking the pseudomonas quinolone signaling system |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875348/ https://www.ncbi.nlm.nih.gov/pubmed/35208954 http://dx.doi.org/10.3390/molecules27041169 |
work_keys_str_mv | AT dastheerthankar halogenateddihydropyrrol2onemoleculesinhibitpyocyaninbiosynthesisbyblockingthepseudomonasquinolonesignalingsystem AT sabirshekh halogenateddihydropyrrol2onemoleculesinhibitpyocyaninbiosynthesisbyblockingthepseudomonasquinolonesignalingsystem AT chenren halogenateddihydropyrrol2onemoleculesinhibitpyocyaninbiosynthesisbyblockingthepseudomonasquinolonesignalingsystem AT farrelljessica halogenateddihydropyrrol2onemoleculesinhibitpyocyaninbiosynthesisbyblockingthepseudomonasquinolonesignalingsystem AT krielfrederikh halogenateddihydropyrrol2onemoleculesinhibitpyocyaninbiosynthesisbyblockingthepseudomonasquinolonesignalingsystem AT whiteleygregorys halogenateddihydropyrrol2onemoleculesinhibitpyocyaninbiosynthesisbyblockingthepseudomonasquinolonesignalingsystem AT glasbeytrevoro halogenateddihydropyrrol2onemoleculesinhibitpyocyaninbiosynthesisbyblockingthepseudomonasquinolonesignalingsystem AT manosjim halogenateddihydropyrrol2onemoleculesinhibitpyocyaninbiosynthesisbyblockingthepseudomonasquinolonesignalingsystem AT willcoxmarkdp halogenateddihydropyrrol2onemoleculesinhibitpyocyaninbiosynthesisbyblockingthepseudomonasquinolonesignalingsystem AT kumarnaresh halogenateddihydropyrrol2onemoleculesinhibitpyocyaninbiosynthesisbyblockingthepseudomonasquinolonesignalingsystem |