title: Functionality of Borrelia burgdorferi LuxS: the Lyme disease spirochete produces and responds to the pheromone autoinducer-2 and lacks a complete activated-methyl cycle.
abstract: Borrelia burgdorferi produces Pfs and LuxS enzymes for breakdown of the toxic byproducts of methylation reactions, producing 4,5-dihydroxy-2,3-pentanedione (DPD), adenine, and homocysteine. DPD and its spontaneously rearranged derivatives constitute a class of bacterial pheromones named autoinducer-2 (AI-2). We describe that B. burgdorferi produces DPD during laboratory cultivation. Furthermore, addition of in vitro synthesized DPD to cultured B. burgdorferi resulted in altered expression levels of a specific set of bacterial proteins, among which is the outer surface lipoprotein VlsE. While a large number of bacteria utilize homocysteine, the other LuxS product, for synthesis of methionine as part of the activated-methyl cycle, B. burgdorferi was found to lack that ability. We propose that the main function of B. burgdorferi LuxS is to synthesize DPD and that the Lyme disease spirochete utilizes a form of DPD as a pheromone to control gene expression.
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, College of Medicine, University of Kentucky, MS 415 Chandler Medical Center, Lexington, Kentucky 40536-0298, USA.
authors.forename: Kate
authors.initials: K
authors.lastname: von Lackum
authors.forename: Kelly
authors.initials: K
authors.lastname: Babb
authors.forename: Sean P
authors.initials: SP
authors.lastname: Riley
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Wattier
authors.forename: Tomasz
authors.initials: T
authors.lastname: Bykowski
authors.forename: Brian
authors.initials: B
authors.lastname: Stevenson
mesh_terms: D000942:Antigens, Bacterial / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000187:drug effects / Q000201:enzymology*; D013437:Carbon-Sulfur Lyases; D015964:Gene Expression Regulation, Bacterial; D006714:Homoserine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000494:pharmacology; D007783:Lactones / Q000494:pharmacology*; D008074:Lipoproteins / Q000096:biosynthesis; D008715:Methionine / Q000378:metabolism; D010420:Pentanes / Q000378:metabolism*; D010675:Pheromones / Q000502:physiology*
chemical_list: C493138:4,5-dihydroxy-2,3-pentanedione; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007783:Lactones; D008074:Lipoproteins; C091088:N-octanoylhomoserine lactone; D010420:Pentanes; D010675:Pheromones; C105546:VlsE protein, Borrelia burgdorferi; D006714:Homoserine; D008715:Methionine; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria