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Infection and Immunity, August 2005, p. 4972-4981, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4972-4981.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Borrelia burgdorferi rel Is Responsible for Generation of Guanosine-3'-Diphosphate-5'-Triphosphate and Growth Control

Julia V. Bugrysheva,¹ Anton V. Bryksin,¹ Henry P. Godfrey,² and Felipe C. Cabello^1*

Departments of Microbiology and Immunology,¹ Pathology, New York Medical College, Valhalla, New York 10595²

Received 11 January 2005/ Returned for modification 1 March 2005/ Accepted 14 March 2005

The global transcriptional regulator (p)ppGpp (guanosine-3'-diphosphate-5'-triphosphate and guanosine-3',5'-bisphosphate, collectively) produced by the relA and spoT genes in Escherichia coli allows bacteria to adapt to different environmental stresses. The genome of Borrelia burgdorferi encodes a single chromosomal rel gene (BB0198) (B. burgdorferi rel [rel_Bbu]) homologous to relA and spoT of E. coli. Its role in (p)ppGpp synthesis, bacterial growth, and modulation of gene expression has not been studied in detail. We constructed a rel_Bbu deletion mutant in an infectious B. burgdorferi 297 strain and isolated an extrachromosomally complemented derivative of this mutant. The mutant did not synthesize rel_Bbu mRNA, Rel_Bbu protein, or (p)ppGpp. This synthesis was restored in the complemented derivative, confirming that rel_Bbu is necessary and sufficient for (p)ppGpp synthesis and degradation in B. burgdorferi. The rel_Bbu mutant grew well during log phase in complete BSK-H but reached lower cell concentrations in the stationary phase than the wild-type parent, suggesting that (p)ppGpp may be an important factor in the ability of B. burgdorferi to adapt to stationary phase. Deletion of rel_Bbu did not eliminate the temperature-elicited OspC shift, nor did it alter bmp gene expression or B. burgdorferi antibiotic susceptibility. Although deletion of rel_Bbu eliminated B. burgdorferi virulence for mice, which was not restored by complementation, we suggest that rel_Bbu-dependent accumulation of (p)ppGpp may be important for in vivo survival of this pathogen.

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* Corresponding author. Mailing address: Department of Microbiology and Immunology, Basic Science Building, New York Medical College, Valhalla, NY 10595. Phone: (914) 594-4182. Fax: (914) 594-4176. E-mail: cabello{at}nymc.edu.

Editor: D. L. Burns

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Infection and Immunity, August 2005, p. 4972-4981, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4972-4981.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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