Halogenated furanones inhibit quorum sensing through accelerated LuxR turnover.
N-acyl-L-homoserine lactones (AHLs) are co-regulatory ligands required for control of the expression of genes encoding virulence traits in many Gram-negative bacterial species. Recent studies have indicated that AHLs modulate the cellular concentrations of LuxR-type regulatory proteins by binding and fortifying these proteins against proteolytic degradation (Zhu & Winans, 2001 ). Halogenated furanones produced by the macroalga Delisea pulchra inhibit AHL-dependent gene expression. This study assayed for an in vivo interaction between a tritiated halogenated furanone and the LuxR protein of Vibrio fischeri overproduced in Escherichia coli. Whilst a stable interaction between the algal metabolite and the bacterial protein was not found, it was noted by Western analysis that the half-life of the protein is reduced up to 100-fold in the presence of halogenated furanones. This suggests that halogenated furanones modulate LuxR activity but act to destabilize, rather than protect, the AHL-dependent transcriptional activator. The furanone-dependent reduction in the cellular concentration of the LuxR protein was associated with a reduction in expression of a plasmid encoded P(luxI)-gfp(ASV) fusion suggesting that the reduction in LuxR concentration is the mechanism by which furanones control expression of AHL-dependent phenotypes. The mode of action by which halogenated furanones reduce cellular concentrations of the LuxR protein remains to be characterized.
Manefield
Michael
M
Department of Microbiology, Technical University of Denmark, 2800 Lyngby, Denmark2.|School of Microbiology and Immunology, University of New South Wales, Sydney, Australia1.
Rasmussen
Thomas Bovbjerg
TB
Department of Microbiology, Technical University of Denmark, 2800 Lyngby, Denmark2.
Henzter
Morten
M
Department of Microbiology, Technical University of Denmark, 2800 Lyngby, Denmark2.
Andersen
Jens Bo
JB
Department of Microbiology, Technical University of Denmark, 2800 Lyngby, Denmark2.
Steinberg
Peter
P
Centre for Marine Biofouling and Bio-Innovation, University of New South Wales, Sydney, Australia3.
Kjelleberg
Staffan
S
Centre for Marine Biofouling and Bio-Innovation, University of New South Wales, Sydney, Australia3.|School of Microbiology and Immunology, University of New South Wales, Sydney, Australia1.
Givskov
Michael
M
Department of Microbiology, Technical University of Denmark, 2800 Lyngby, Denmark2.
D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D005663:Furans / Q000494:pharmacology*; D015964:Gene Expression Regulation, Bacterial; D007700:Kinetics; D012097:Repressor Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D014733:Vibrio / Q000235:genetics / Q000502:physiology
D005663:Furans; D012097:Repressor Proteins; D015534:Trans-Activators; C064778:LuxR autoinducer binding proteins