Borrelia burgdorferi Harbors a Transport System Essential for Purine Salvage and Mammalian Infection

Abstract

ABSTRACTBorrelia burgdorferiis the tick-borne bacterium that causes the multistage inflammatory disease Lyme disease.B. burgdorferihas a reduced genome and lacks the enzymes required forde novosynthesis of purines for synthesis of RNA and DNA. Therefore, this obligate pathogen is dependent upon the tick vector and mammalian host environments for salvage of purine bases for nucleic acid biosynthesis. This pathway is vital forB. burgdorferisurvival throughout its infectious cycle, as key enzymes in the purine salvage pathway are essential for the ability of the spirochete to infect mice and critical for spirochete replication in the tick. The transport of preformed purines into the spirochete is the first step in the purine salvage pathway and may represent a novel therapeutic target and/or means to deliver antispirochete molecules to the pathogen. However, the transport systems critical for purine salvage byB. burgdorferihave yet to be identified. Herein, we demonstrate that the genesbbb22andbbb23, present onB. burgdorferi's essential plasmid circular plasmid 26 (cp26), encode key purine transport proteins. BBB22 and/or BBB23 is essential for hypoxanthine transport and contributes to the transport of adenine and guanine. Furthermore,B. burgdorferilackingbbb22-23was noninfectious in mice up to a dose of 1 × 107spirochetes. Together, our data establish thatbbb22-23encode purine permeases critical forB. burgdorferimammalian infectivity, suggesting that this transport system may serve as a novel antimicrobial target for the treatment of Lyme disease.