Dataset Information

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

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 Chlamydia trachomatis 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 trpRBA tryptophan salvage pathway in C. trachomatis. Iron starvation specifically induces trpBA expression from a novel promoter element within an intergenic region flanked by trpR and trpB. YtgR, the only known iron-dependent regulator in Chlamydia, can bind to the trpRBA intergenic region upstream of the alternative trpBA promoter to repress transcription. Simultaneously, YtgR binding promotes the termination of transcripts from the primary promoter upstream of trpR. 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 Chlamydia.

SUBMITTER: Pokorzynski ND

PROVIDER: S-EPMC6504234 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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

Pokorzynski Nick D ND Brinkworth Amanda J AJ Carabeo Rey R

eLife 20190402

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 Chlamydia trachomatis 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 trpRBA tryptophan salvage pathway in C. trachomatis. Iron starvation spe ...[more]

PMID: 30938288

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Project description:Iron is essential for growth and development of Chlamydia. Its long-term starvation in cultured mammalian cells leads to production of aberrant noninfectious chlamydial forms, also known as persistence. Immediate transcriptional responses to iron limitation have not been characterized, leaving a knowledge gap of how Chlamydia regulates its response to changes in iron availability. We used the fast-chelating agent 2,2'-bipyridyl (BPDL) to homogeneously starve Chlamydia trachomatis serovar L2 of iron, starting at 6 or 12 h postinfection. Immediate transcriptional responses were monitored after only 3 or 6 h of BPDL treatment, well before formation of aberrant Chlamydia. The first genomewide transcriptional response of C. trachomatis to iron starvation was subsequently determined utilizing RNA sequencing. Only 7% and 8% of the genome were differentially expressed in response to iron starvation at the early and middle stages of development, respectively. Biological pathway analysis revealed an overarching theme. Synthesis of macromolecular precursors (deoxynucleotides, amino acids, charged tRNAs, and acetyl coenzyme A [acetyl-CoA]) was upregulated, while energy-expensive processes (ABC transport and translation) were downregulated. A large fraction of differentially downregulated genes are involved in translation, including those encoding ribosome assembly and initiation and termination factors, which could be analogous to the translation downregulation triggered by stress in other prokaryotes during stringent responses. Additionally, transcriptional upregulation of DNA repair, oxidative stress, and tryptophan salvage genes reveals a possible coordination of responses to multiple antimicrobial and immunological insults. These responses of replicative-phase Chlamydia to iron starvation indicate a prioritization of survival over replication, enabling the pathogen to "stock the pantry" with ingredients needed for rapid growth once optimal iron levels are restored. IMPORTANCE By utilizing an experimental approach that monitors the immediate global response of Chlamydia trachomatis to iron starvation, clues to long-standing issues in Chlamydia biology are revealed, including how Chlamydia adapts to this stress. We determined that this pathogen initiates a transcriptional program that prioritizes replenishment of nutrient stores over replication, possibly in preparation for rapid growth once optimal iron levels are restored. Transcription of genes for biosynthesis of metabolic precursors was generally upregulated, while those involved in multiple steps of translation were downregulated. We also observed an increase in transcription of genes involved in DNA repair and neutralizing oxidative stress, indicating that Chlamydia employs an "all-or-nothing" strategy. Its small genome limits its ability to tailor a specific response to a particular stress. Therefore, the "all-or-nothing" strategy may be the most efficient way of surviving within the host, where the pathogen likely encounters multiple simultaneous immunological and nutritional insults.

Dataset Information

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

Publications

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

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