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

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12 Citations (Scopus)

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 languageEnglish
Article number1169
Number of pages14
JournalMolecules
Volume27
Issue number4
DOIs
Publication statusPublished - 1 Feb 2022
Externally publishedYes

Keywords

  • Dihydropyrrol-2-one
  • LasR
  • P. aeruginosa
  • PQS
  • Pyocyanin
  • Quorum sensing

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