A bipartite iron-dependent transcriptional regulation of the tryptophan salvage pathway in <i>Chlamydia trachomatis</i>.

Abstract

During infection, pathogens are starved of essential nutrients such as iron and tryptophan by host immune effectors. Without conserved global stress response regulators, how the obligate intracellular bacterium <i>Chlamydia trachomatis</i> arrives at a physiologically similar 'persistent' state in response to starvation of either nutrient remains unclear. Here, we report on the iron-dependent regulation of the <i>trpRBA</i> tryptophan salvage pathway in <i>C. trachomatis.</i> Iron starvation specifically induces <i>trpBA</i> expression from a novel promoter element within an intergenic region flanked by <i>trpR</i> and <i>trpB</i>. YtgR, the only known iron-dependent regulator in <i>Chlamydia</i>, can bind to the <i>trpRBA</i> intergenic region upstream of the alternative <i>trpBA</i> promoter to repress transcription. Simultaneously, YtgR binding promotes the termination of transcripts from the primary promoter upstream of <i>trpR</i>. This is the first description of an iron-dependent mechanism regulating prokaryotic tryptophan biosynthesis that may indicate the existence of novel approaches to gene regulation and stress response in <i>Chlamydia.</i>