Abstract
The trp operon of Chlamydia trachomatis is organized differently from other model bacteria. It contains trpR, an intergenic region (IGR), and the biosynthetic trpB and trpA open-reading frames. TrpR is a tryptophan-dependent repressor that regulates the major promoter (PtrpR), while the IGR harbors an alternative promoter (PtrpBA) and an operator sequence for the iron-dependent repressor YtgR to regulate trpBA expression. Here, we report that YtgR repression at PtrpBA is also dependent on tryptophan by regulating YtgR levels through a rare triple-tryptophan motif (WWW) in the YtgCR precursor. Inhibiting translation during tryptophan limitation at the WWW motif subsequently promotes Rho-independent transcription termination of ytgR, thereby de-repressing PtrpBA. Thus, YtgR represents an alternative strategy to attenuate trpBA expression, expanding the repertoire for trp operon attenuation beyond TrpL- and TRAP-mediated mechanisms described in other bacteria. Furthermore, repurposing the iron-dependent repressor YtgR underscores the fundamental importance of maintaining tryptophan-dependent attenuation of the trpRBA operon.
Highlights
The trp operon of Chlamydia trachomatis is organized differently from other model bacteria
We tested these hypotheses by analyzing trpRBA transcript expression by reverse transcription quantitative PCR (RT-qPCR) under ironor tryptophan-limited conditions
TrpBA expression from the same nucleotide position as iron limitation, 512,005. These data implied that trpBA is transcribed from the same YtgR-regulated promoter, PtrpBA, in response to both iron and tryptophan limitation (Fig. 6). These data collectively point to a model where tryptophan deprivation limits the level of the YtgR repressor to activate transcription from the alternative YtgR-regulated promoter for trpBA (Fig. 6)
Summary
The trp operon of Chlamydia trachomatis is organized differently from other model bacteria. IDO1 catabolizes tryptophan to N-formylkynurenine[2], thereby depriving pathogens of host-derived tryptophan Intracellular bacteria such as Mycobacterium tuberculosis and Francisella tularensis are insensitive to immunological tryptophan depletion which is dependent on their ability to biosynthesize tryptophan[3,4]. Several obligate intracellular human parasites are natural tryptophan auxotrophs, including the Gram-negative bacterium Chlamydia trachomatis (Ctr), rendering these pathogens susceptible to IFNγ-mediated tryptophan depletion[5,6,7,8]. This raises the intriguing question of how such pathogens respond to tryptophan deprivation to survive. In the model bacterium Escherichia coli, the trpEDCBA operon is regulated by two complementary mechanisms: TrpRmediated tryptophan-dependent transcriptional repression[26] and
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