Functions of T. pallidum and L. interrogans PUR Proteins

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The pathogenic spirochetes Treponema pallidum (syphilis) and Leptospira interrogans (leptospirosis) change their protein compositions during infection processes, evidently as means to adapt to different niches. Despite the significance of these two diseases, essentially nothing is known about how either bacterium regulates gene expression. Complicating matters, there are no methods to genetically manipulate T. pallidum, and the genetic toolbox for L. interrogans is largely limited to random mutagenesis. In our studies of a related spirochete, Borrelia burgdorferi (Lyme disease), we discovered a differentially expressed DNA- and RNA-binding protein named BpuR, which, in turn, controls expression of numerous genes and proteins. Mutant B. burgdorferi that are unable to control BpuR levels are severely attenuated for mammalian infection. The protein’s name derives from its “PUR”-domain, a motif also found in crucial regulatory proteins of humans and all other higher eukaryotes, as well as many pathogenic bacterial species. Both T. pallidum and L. interrogans encode a PUR-domain protein, which we named TpuR and LpuR, respectively. We hypothesize that TpuR and LpuR will bind specific sequences in their respective DNA and RNA, as does every other known PUR-domain protein. In silico analyses will then be applied to identify potential PUR protein-binding sites within each species’ genome, and a subset of putative binding sites will be experimentally validated. We further hypothesize that T. pallidum and L. interrogans control production of their PUR proteins, and that PUR protein levels correlate with differential expression of genes that contain PUR protein-binding sites adjacent to their promoters. We predict that this combination of computational, biochemical, and in vivo analyses will provide insight into regulatory mechanisms employed by these two pathogens, important steps toward understanding the bacteria’s infectious properties and development of therapies that specifically block adaptation to their human hosts.
Effective start/end date6/15/165/31/19


  • National Institute of Allergy and Infectious Diseases: $147,640.00


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