Halogenated dihydropyrrol-2-one molecules inhibit pyocyanin biosynthesis by blocking the pseudomonas quinolone signaling system

Theerthankar Das; Shekh Sabir; Ren Chen; Jessica Farrell; Frederik H. Kriel; Gregory S. Whiteley; Trevor O. Glasbey; Jim Manos; Mark D. P. Willcox; Naresh Kumar

doi:10.3390/molecules27041169

Halogenated dihydropyrrol-2-one molecules inhibit pyocyanin biosynthesis by blocking the pseudomonas quinolone signaling system

Theerthankar Das, Shekh Sabir, Ren Chen, Jessica Farrell, Frederik H. Kriel, Gregory S. Whiteley, Trevor O. Glasbey, Jim Manos, Mark D. P. Willcox, Naresh Kumar

Western Sydney University

Research output: Contribution to journal › Article › peer-review

Abstract

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 halo-genated 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 produc-tion, 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.

Original language	English
Article number	1169
Number of pages	14
Journal	Molecules
Volume	27
Issue number	4
DOIs	https://doi.org/10.3390/molecules27041169
Publication status	Published - 2022

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© 2022 by the authors. 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/).

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title = "Halogenated dihydropyrrol-2-one molecules inhibit pyocyanin biosynthesis by blocking the pseudomonas quinolone signaling system",

abstract = "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 halo-genated 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 produc-tion, 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.",

author = "Theerthankar Das and Shekh Sabir and Ren Chen and Jessica Farrell and Kriel, {Frederik H.} and Whiteley, {Gregory S.} and Glasbey, {Trevor O.} and Jim Manos and Willcox, {Mark D. P.} and Naresh Kumar",

year = "2022",

doi = "10.3390/molecules27041169",

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T1 - Halogenated dihydropyrrol-2-one molecules inhibit pyocyanin biosynthesis by blocking the pseudomonas quinolone signaling system

AU - Das, Theerthankar

AU - Sabir, Shekh

AU - Chen, Ren

AU - Farrell, Jessica

AU - Kriel, Frederik H.

AU - Whiteley, Gregory S.

AU - Glasbey, Trevor O.

AU - Manos, Jim

AU - Willcox, Mark D. P.

AU - Kumar, Naresh

PY - 2022

Y1 - 2022

N2 - 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 halo-genated 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 produc-tion, 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.

AB - 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 halo-genated 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 produc-tion, 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.

UR - https://hdl.handle.net/1959.7/uws:75557

U2 - 10.3390/molecules27041169

DO - 10.3390/molecules27041169

M3 - Article

SN - 1420-3049

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JO - Molecules

JF - Molecules

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ER -

Halogenated dihydropyrrol-2-one molecules inhibit pyocyanin biosynthesis by blocking the pseudomonas quinolone signaling system

Abstract

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