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B orrelia host ad aptation R egulator ( BadR ) regulates rpoS to modulate host adaptation and virulence factors in B orrelia burgdorferi
Author(s) -
Miller Christine L.,
Karna S. L. Rajasekhar,
Seshu J.
Publication year - 2013
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12171
Subject(s) - rpos , biology , borrelia burgdorferi , virulence , repressor , host adaptation , genetics , microbiology and biotechnology , gene , transcription factor , promoter , gene expression , antibody
Summary The RpoS transcription factor of B orrelia 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 ( B orrelia host ad aptation R egulator), 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.