RT Journal Article SR Electronic T1 The tryptophan salvage pathway is dynamically regulated by the iron-dependent repressor YtgR in Chlamydia trachomatis JF bioRxiv FD Cold Spring Harbor Laboratory SP 322586 DO 10.1101/322586 A1 Nick D. Pokorzynski A1 Rey A. Carabeo YR 2018 UL http://biorxiv.org/content/early/2018/05/15/322586.1.abstract AB Mammalian hosts restrict cellular nutrient availability to starve invading pathogens and successfully clear an infection by a process termed “nutritional immunity”. For the obligate intracellular pathogen Chlamydia trachomatis, nutritional immunity likely encompasses the simultaneous limitation of the amino acid tryptophan and the essential biometal iron. Unlike other model bacteria, C. trachomatis lacks many global stress response systems - such as “stringent response” homologs - adapted to these host insults. However, a physiological response by Chlamydia that is common to both stresses is the development of an aberrant, “persistent” state, suggesting that tryptophan and iron starvation trigger a coordinated developmental program. Here, we report that the trpRBA operon for tryptophan salvage in C. trachomatis serovar L2 is regulated at the transcriptional level by iron. The expression of the tryptophan synthase encoding genes, trpBA, is induced following iron limitation while that of the repressor trpR is not. We show that this specific induction of trpBA expression initiates from a novel promoter element within an intergenic region flanked by trpR and trpB. YtgR, a DtxR-homolog and the only known iron-dependent transcriptional regulator in Chlamydia, can bind to the trpRBA intergenic region upstream of the alternative trpBA promoter to repress transcription. This binding also likely attenuates transcription from the primary promoter upstream of trpR by blocking RNA polymerase read-through. These data illustrate a dynamic and integrated method of regulating tryptophan biosynthesis in an iron-dependent manner, which has not been described in any other prokaryote, underscoring the uniqueness of Chlamydia.