title: Borrelia host adaptation Regulator (BadR) regulates rpoS to modulate host adaptation and virulence factors in Borrelia burgdorferi.
abstract: The RpoS transcription factor of Borrelia burgdorferi is a 'gatekeeper' because it activates genes required for spirochaetes to transition from tick to vertebrate hosts. However, it remains unknown how RpoS becomes repressed to allow the spirochaetes to transition back from the vertebrate host to the tick vector. Here we show that a putative carbohydrate-responsive regulatory protein, designated BadR (Borrelia host adaptation Regulator), is a transcriptional repressor of rpoS. BadR levels are elevated in B. burgdorferi cultures grown under in vitro conditions mimicking unfed-ticks and badR-deficient strains are defective for growth under these same conditions. Microarray and immunoblot analyses of badR-deficient strains showed upregulation of rpoS and other factors important for virulence in vertebrate hosts, as well as downregulation of putative tick-specific determinants (e.g. linear plasmid 28-4 genes). DNA-binding assays revealed BadR binds to upstream regions of rpoS. Site-directed mutations in BadR and the presence of phosphorylated sugars affected BadR's binding to the rpoS promoters. badR-deficient B. burgdorferi were unable to colonize mice. Several putative tick-specific targets have been identified. Our study identified a novel regulator, BadR, and provides a link between nutritional environmental cues utilized by spirochaetes to adaptation to disparate conditions found in the tick and vertebrate hosts.
authors: South Texas Center for Emerging Infectious Diseases, Center for Excellence in Infection Genomics and Department of Biology, The University of Texas at San Antonio, San Antonio, Texas, USA.
authors: Christine L
authors: CL
authors: Miller
authors: S L Rajasekhar
authors: SL
authors: Karna
authors: J
authors: J
authors: Seshu
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D025065:Borrelia burgdorferi / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity* / Q000502:physiology*; D015536:Down-Regulation / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial / Q000235:genetics; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000378:metabolism; D012808:Sigma Factor / Q000378:metabolism*; D013045:Species Specificity; D013987:Ticks / Q000382:microbiology; D015854:Up-Regulation / Q000235:genetics; D037521:Virulence Factors / Q000378:metabolism*; D014994:Xylose / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D012097:Repressor Proteins; D012808:Sigma Factor; D037521:Virulence Factors; C069567:sigma factor KatF protein, Bacteria; D014994:Xylose
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