title: An unexpected switch in the modulation of AI-2-based quorum sensing discovered through synthetic 4,5-dihydroxy-2,3-pentanedione analogues.
abstract: Quorum sensing (QS) has traditionally referred to a mechanism of communication within a species of bacteria. However, emerging research implicates QS in interspecies communication and competition, and such systems have been proposed in a wide variety of bacteria. The AI-2-based QS system represents the most studied of these proposed interspecies systems, and has been proposed to regulate diverse functions such as bioluminescence, expression of virulence factors, and biofilm formation. As such, the development of modulatory compounds, both agonists and antagonists, is of great interest for the treatment of bacterial infections and the study of unknown AI-2-based QS systems. Toward this end, we have designed and synthesized a panel of 4,5-dihydroxy-2,3-pentanedione/AI-2 analogues and evaluated their effects on the AI-2 QS of various bacteria. The panel of compounds exhibited differential effects in the bacterial cell lines examined, providing a platform for the development of broad-spectrum modulators of AI-2-based QS.
authors.affiliation: The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Colin A
authors.initials: CA
authors.lastname: Lowery
authors.forename: Junguk
authors.initials: J
authors.lastname: Park
authors.forename: Gunnar F
authors.initials: GF
authors.lastname: Kaufmann
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
mesh_terms: D004790:Enzyme Induction; D006714:Homoserine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D007783:Lactones / Q000737:chemistry / Q000378:metabolism*; D008163:Luminescent Measurements; D010422:Pentanones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D053038:Quorum Sensing / Q000187:drug effects*; D012486:Salmonella typhimurium / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D014733:Vibrio / Q000378:metabolism / Q000502:physiology; D001616:beta-Galactosidase / Q000096:biosynthesis
chemical_list: D007783:Lactones; C091088:N-octanoylhomoserine lactone; D010422:Pentanones; D006714:Homoserine; D001616:beta-Galactosidase