Title

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

Authors

Authors

S. Jain; S. Sutchu; P. A. Rosa; R. Byram;M. W. Jewett

Comments

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Abbreviated Journal Title

Infect. Immun.

Keywords

LYME-DISEASE SPIROCHETE; BACILLUS-SUBTILIS; ESCHERICHIA-COLI; PURR; REGULON; PROTEIN; PLASMID; CYCLE; OSPC; PREDICTION; CHITOBIOSE; Immunology; Infectious Diseases

Abstract

Borrelia burgdorferi is the tick-borne bacterium that causes the multistage inflammatory disease Lyme disease. B. burgdorferi has a reduced genome and lacks the enzymes required for de novo synthesis 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 for B. burgdorferi survival 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 by B. burgdorferi have yet to be identified. Herein, we demonstrate that the genes bbb22 and bbb23, present on B. 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. burgdorferi lacking bbb22-23 was noninfectious in mice up to a dose of 1 x 10(7) spirochetes. Together, our data establish that bbb22-23 encode purine permeases critical for B. burgdorferi mammalian infectivity, suggesting that this transport system may serve as a novel antimicrobial target for the treatment of Lyme disease.

Journal Title

Infection and Immunity

Volume

80

Issue/Number

9

Publication Date

1-1-2012

Document Type

Article

Language

English

First Page

3086

Last Page

3093

WOS Identifier

WOS:000307869100011

ISSN

0019-9567

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