Small molecule inhibitors of bacterial quorum sensing and biofilm formation.
Bacteria monitor their local population densities using small molecules (or autoinducers) in a process known as quorum sensing. Here, we report a new and efficient synthetic route to naturally occurring bacterial autoinducers [N-acyl l-homoserine lactones (AHLs)] that is readily amenable to the synthesis of analogues. This route has been applied in the first synthesis of a library of non-native AHLs. Evaluation of these compounds in bacterial reporter gene and biofilm assays has revealed a potent set of quorum sensing antagonists. These ligands will serve as valuable new tools to explore the role of quorum sensing in bacterial pathogenesis.
Geske
Grant D
GD
Department of Chemistry, University of Wisconsin--Madison, 1101 University Avenue, Madison, Wisconsin 53706, USA.
Wezeman
Rachel J
RJ
Siegel
Adam P
AP
Blackwell
Helen E
HE
D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006714:Homoserine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D008872:Microwaves; D008968:Molecular Conformation; D011550:Pseudomonas aeruginosa / Q000187:drug effects
D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D007783:Lactones; D008024:Ligands; D006714:Homoserine