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CT406 Encodes a Chlamydial Ortholog of NrdR, a Repressor of Ribonucleotide Reductase ▿

By Elizabeth Di Russo Case, Johnny C. Akers and Ming Tan


Chlamydia trachomatisis an obligate intracellular bacterium that is dependent on its host cell for nucleotides. Chlamydiaimports ribonucleotide triphosphates (NTPs) but not deoxyribonucleotide triphosphates (dNTPs) and instead uses ribonucleotide reductase to convert imported ribonucleotides into deoxyribonucleotides for DNA synthesis. The genes encoding ribonucleotide reductase have been recently shown to be negatively controlled by a conserved regulator called NrdR. In this study, we provide direct evidence that Escherichia coliNrdR is a transcriptional repressor and that C. trachomatisCT406 encodes its chlamydial ortholog. We showed that CT406 binds specifically to two NrdR boxes upstream of the nrdABoperon in C. trachomatis. Using an in vitrotranscription assay, we confirmed that these NrdR boxes function as an operator since they were necessary and sufficient for CT406-mediated repression. We validated our in vitrofindings with reporter studies in E. colishowing that both E. coliNrdR and CT406 repressed transcription from the E. colinrdHand C. trachomatisnrdABpromoters in vivo. This in vivorepression was reversed by hydroxyurea treatment. Since hydroxyurea inhibits ribonucleotide reductase and reduces intracellular deoxyribonucleotide levels, these results suggest that NrdR activity is modulated by a deoxyribonucleotide corepressor

Topics: Molecular Biology of Pathogens
Publisher: American Society for Microbiology
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Provided by: PubMed Central
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