N-Sulfonyl homoserine lactones as antagonists of bacterial quorum sensing.
A series of 11 new analogues of N-acylhomoserine lactones in which the carboxamide bond was replaced by a sulfonamide one, has been synthesised. These compounds were evaluated for their ability to competitively inhibit the action of 3-oxohexanoyl-L-homoserine lactone, the natural ligand of the quorum sensing transcriptional regulator LuxR, which in turn activates expression of bioluminescence in the model bacterium Vibrio fischeri. Several compounds were found to display antagonist activity. Molecular modeling suggests that the latter prevent a cascade of structural rearrangements necessary for the formation of the active LuxR dimer.
Castang
Sandra
S
Unité de Microbiologie et Génétique, UMR CNRS-INSA-UCB 5122, Bât. A. Lwoff, UCB, 69622 Villeurbanne, France.
Chantegrel
Bernard
B
Deshayes
Christian
C
Dolmazon
René
R
Gouet
Patrice
P
Haser
Richard
R
Reverchon
Sylvie
S
Nasser
William
W
Hugouvieux-Cotte-Pattat
Nicole
N
Doutheau
Alain
A
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000737:chemistry; D048908:Aliivibrio fischeri / Q000187:drug effects; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D019281:Dimerization; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D006714:Homoserine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008163:Luminescent Measurements; D008958:Models, Molecular; D008969:Molecular Sequence Data; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism
D000900:Anti-Bacterial Agents; D007783:Lactones; C091088:N-octanoylhomoserine lactone; D012097:Repressor Proteins; D013449:Sulfonamides; D015534:Trans-Activators; C064778:LuxR autoinducer binding proteins; D006714:Homoserine; C030654:N-(3-oxohexanoyl)-3-aminodihydro-2(3H)-furanone; D015107:4-Butyrolactone