TY - JOUR
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
N1 - Funding Information:
Funding: This research was funded by the Department of Industry, Innovation and Science (Innovative Manufacturing CRC Ltd.), Australia and Whiteley Corporation, NSW, Australia co-funded project grant A Novel approach to Biofilm Disruption and Removal, grant number IMCRC/WLY/08052019.1. The work was supported by a Discovery Project from the Australian Research Council grant DP180100845.
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/2/1
Y1 - 2022/2/1
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.
KW - Dihydropyrrol-2-one
KW - LasR
KW - P. aeruginosa
KW - PQS
KW - Pyocyanin
KW - Quorum sensing
UR - http://www.scopus.com/inward/record.url?scp=85124590174&partnerID=8YFLogxK
U2 - 10.3390/molecules27041169
DO - 10.3390/molecules27041169
M3 - Article
C2 - 35208954
AN - SCOPUS:85124590174
SN - 1420-3049
VL - 27
JO - Molecules
JF - Molecules
IS - 4
M1 - 1169
ER -