Regulation of an iron-dependent repressor by tryptophan availability attenuates transcription of the tryptophan salvage genes inChlamydia trachomatis

Abstract

The trp operon of Chlamydia trachomatis has a genetic organization that is distinct from other model bacteria. The operon contains the trpR open-reading frame (ORF), an intergenic region (IGR), and the trpB and trpA ORFs. TrpR mediates tryptophan-dependent regulation of the operon from the major promoter upstream of trpR (PtrpR). We recently reported that trpBA is additionally regulated by the iron-dependent repressor YtgR via an operator sequence within the IGR upstream of an alternative promoter for TrpR-independent trpBA expression (PtrpBA). Here we report that YtgR repression of PtrpBA is also dependent on tryptophan levels via a rare triple-tryptophan motif (WWW) in the N-terminal permease domain of the YtgCR precursor. Tryptophan limitation inhibits translation at the WWW motif and subsequently promotes transcription termination of ytgCR in a Rho-independent manner. This regulatory schematic resembles mechanisms of transcriptional attenuation for trp operons described in model bacteria, such as cis-attenuation by TrpL in E. coli or trans-attenuation by TRAP in B. subtilis. YtgR performs an analogous function by sensing both iron and tryptophan levels, with the latter highlighting the unique strategy of Chlamydia to retain a trans-attenuator mechanism for regulating expression of the trpRBA operon.