Synthesis of autoinducer 2 by the lyme disease spirochete, Borrelia burgdorferi.
Defining the metabolic capabilities and regulatory mechanisms controlling gene expression is a valuable step in understanding the pathogenic properties of infectious agents such as Borrelia burgdorferi. The present studies demonstrated that B. burgdorferi encodes functional Pfs and LuxS enzymes for the breakdown of toxic products of methylation reactions. Consistent with those observations, B. burgdorferi was shown to synthesize the end product 4,5-dihydroxy-2,3-pentanedione (DPD) during laboratory cultivation. DPD undergoes spontaneous rearrangements to produce a class of pheromones collectively named autoinducer 2 (AI-2). Addition of in vitro-synthesized DPD to cultured B. burgdorferi resulted in differential expression of a distinct subset of proteins, including the outer surface lipoprotein VlsE. Although many bacteria can utilize the other LuxS product, homocysteine, for regeneration of methionine, B. burgdorferi was found to lack such ability. It is hypothesized that B. burgdorferi produces LuxS for the express purpose of synthesizing DPD and utilizes a form of that molecule as an AI-2 pheromone to control gene expression.
Babb
Kelly
K
Dept. of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, Lexington, KY 40536-0298, USA.
von Lackum
Kate
K
Wattier
Rachel L
RL
Riley
Sean P
SP
Stevenson
Brian
B
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000378:metabolism; D001426:Bacterial Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D025065:Borrelia burgdorferi / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D013437:Carbon-Sulfur Lyases; D015180:Electrophoresis, Gel, Two-Dimensional; D015964:Gene Expression Regulation, Bacterial; D006710:Homocysteine / Q000378:metabolism; D006714:Homoserine / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000235:genetics; D007783:Lactones; D008715:Methionine / Q000378:metabolism; D009699:N-Glycosyl Hydrolases / Q000235:genetics / Q000378:metabolism; D010420:Pentanes / Q000378:metabolism; D012329:RNA, Bacterial / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic
C493138:4,5-dihydroxy-2,3-pentanedione; D001426:Bacterial Proteins; D007783:Lactones; C091088:N-octanoylhomoserine lactone; D010420:Pentanes; D012329:RNA, Bacterial; D012333:RNA, Messenger; C112064:VlsII protein, Borrelia burgdorferi; D006710:Homocysteine; D006714:Homoserine; D008715:Methionine; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D009699:N-Glycosyl Hydrolases; C019606:adenosylhomocysteine nucleosidase; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria