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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...

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Autores principales: 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
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
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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.
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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
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