GuaA and GuaB are essential for Borrelia burgdorferi survival in the tick-mouse infection cycle.
Pathogens lacking the enzymatic pathways for de novo purine biosynthesis are required to salvage purines and pyrimidines from the host environment for synthesis of DNA and RNA. Two key enzymes in purine salvage pathways are IMP dehydrogenase (GuaB) and GMP synthase (GuaA), encoded by the guaB and guaA genes, respectively. While these genes are typically found on the chromosome in most bacterial pathogens, the guaAB operon of Borrelia burgdorferi is present on plasmid cp26, which also harbors a number of genes critical for B. burgdorferi viability. Using molecular genetics and an experimental model of the tick-mouse infection cycle, we demonstrate that the enzymatic activities encoded by the guaAB operon are essential for B. burgdorferi mouse infectivity and provide a growth advantage to spirochetes in the tick. These data indicate that the GuaA and GuaB proteins are critical for the survival of B. burgdorferi in the infection cycle and highlight a potential difference in the requirements for purine salvage in the disparate mammalian and tick environments.
Jewett
Mollie W
MW
Laboratory of Zoonotic Pathogens, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases,National Institutes of Health, Hamilton, Montana 59840, USA. jewettm@niaid.nih.gov
Lawrence
Kevin A
KA
Bestor
Aaron
A
Byram
Rebecca
R
Gherardini
Frank
F
Rosa
Patricia A
PA
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000235:genetics / Q000378:metabolism*; D019731:Carbon-Nitrogen Ligases / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D007168:IMP Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D008193:Lyme Disease / Q000382:microbiology / Q000635:transmission*; D051379:Mice; D008809:Mice, Inbred C3H; D016513:Mice, SCID; D009876:Operon; D011687:Purines / Q000378:metabolism; D013987:Ticks / Q000382:microbiology*
D001426:Bacterial Proteins; D011687:Purines; D007168:IMP Dehydrogenase; D019731:Carbon-Nitrogen Ligases; C020828:GMP synthase (glutamine-hydrolyzing)