Genotypic Differences in the<i>Chlamydia pneumoniae tyr</i>P Locus Related to Vascular Tropism and Pathogenicity

Gieffers, Jens; Durling, Luke; Ouellette, Scot P.; Rupp, Jan; Maass, Matthias; Byrne, Gerald I.; Belland, Robert J.

doi:10.1086/378692

Cited by 34 publications

(39 citation statements)

References 26 publications

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“…6). This finding is consistent with the observations in other bacteria that a large molar excess of the corepressor, L-tryptophan, is necessary for negative regulation by TrpR (10,38). We also tested other representative amino acids but found that neither L-tyrosine, Lphenylalanine, L-alanine, L-arginine, L-serine, L-methionine, nor L-proline could function as a corepressor for TrpR (data not shown).…”

Section: Resultssupporting

confidence: 92%

“…The mtr homolog is called tyrP, and it is predicted to encode a tyrosine/tryptophan transporter. There has been particular interest in tyrP because the number of gene copies in C. pneumoniae has been shown to vary according to tissue tropism and disease manifestation (10). So far, however, there is little evidence to indicate that any of these genes are regulated by TrpR in Chlamydia.…”

Section: Discussionmentioning

confidence: 99%

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Molecular Mechanism of Tryptophan-Dependent Transcriptional Regulation inChlamydia trachomatis

Akers¹,

Tan

2006

J Bacteriol

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Tryptophan is an essential amino acid that is required for normal development in Chlamydia species, and tryptophan metabolism has been implicated in chlamydial persistence and tissue tropism. The ability to synthesize tryptophan is not universal among the Chlamydiaceae, but species that have a predicted tryptophan biosynthetic pathway also encode an ortholog of TrpR, a regulator of tryptophan metabolism in many gram-negative bacteria. We show that in Chlamydia trachomatis serovar D, TrpR regulates its own gene and trpB and trpA, the genes for the two subunits of tryptophan synthase. These three genes form an operon that is transcribed by the major form of chlamydial RNA polymerase. TrpR acts as a tryptophan-dependent aporepressor that binds specifically to operator sequences upstream of the trpRBA operon. We also found that TrpR repressed in vitro transcription of trpRBA in a promoter-specific manner, and the level of repression was dependent upon the concentrations of TrpR and tryptophan. Our findings provide a mechanism for chlamydiae to sense changes in tryptophan levels and to respond by modulating expression of the tryptophan biosynthesis genes, and we present a unified model that shows how C. trachomatis can combine transcriptional repression and attenuation to regulate intrachlamydial tryptophan levels. In the face of host defense mechanisms that limit tryptophan availability from the infected cell, the ability to maintain homeostatic control of intrachlamydial tryptophan levels is likely to play an important role in chlamydial pathogenesis.

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Section: Resultssupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Molecular Mechanism of Tryptophan-Dependent Transcriptional Regulation inChlamydia trachomatis

Akers¹,

Tan

2006

J Bacteriol

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“…Tryptophan has been shown to play a pivotal role in chlamydial pathogenesis, and tryptophan limitation induces chlamydiae to enter a persistent growth state (reviewed in reference 18). As another example, strain variation in the tyrP tyrosine/tryptophan permease has been shown to correlate with C. pneumoniae tissue tropism (5). The finding that arginine-dependent regulation is present in only a subset of Chlamydia species suggests that the role of this essential amino acid in species-specific differences in tissue tropism and pathogenesis deserves a closer look.…”

Section: Discussionmentioning

confidence: 99%

Arginine-Dependent Gene Regulation via the ArgR Repressor Is Species Specific inChlamydia

Schaumburg¹,

Tan

2006

J Bacteriol

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Some, but not all, Chlamydia spp. are predicted to encode a homolog of ArgR, a master regulatory molecule that modulates arginine biosynthesis and catabolism in bacteria in response to intracellular arginine levels. While genes for arginine biosynthesis are apparently missing in Chlamydia, a putative arginine transport system encoded by glnP, glnQ, and artJ is present. We found that recombinant Chlamydia pneumoniae ArgR functions as an arginine-dependent aporepressor that bound specifically to operator sequences upstream of the glnPQ operon. ArgR was able to repress transcription in a promoter-specific manner that was dependent on the concentration of the corepressor L-arginine. We were able to locate ArgR operators upstream of glnPQ in C. pneumoniae and Chlamydophila caviae but not Chlamydia trachomatis, which corresponded to the predicted presence or absence of ArgR in these chlamydial species. Our findings indicate that only some members of the family Chlamydiaceae have an arginine-responsive mechanism of gene regulation that is predicted to control arginine uptake from the host cell. This is the first study to directly demonstrate a species-specific mechanism of transcriptional regulation in Chlamydia.

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“…A phylogenetic tree (data not shown) indicates that a gene duplication occurred in the common ancestor of C. trachomatis and C. muridarum. Gieffers et al (40) noted that respiratory strains of Cp. pneumoniae (e.g., strains CW and AR) possessed two paralogous copies of tyrP, whereas vascular strains (e.g., strains J and T) had a single tyrP gene.…”

Section: Self-limitation Of Trp Import Caused By Trp Starvationmentioning

confidence: 99%

“…pneumoniae. It is interesting to consider that whereas the expression of two TyrP paralogs should promote increased competence for Trp import during Trp sufficiency (and this has indeed been shown [40]), it also would increase the Trp burden during Trp insufficiency.…”

Section: Self-limitation Of Trp Import Caused By Trp Starvationmentioning

confidence: 99%

The AlternativeTranslational Profile That Underlies the Immune-Evasive State of Persistence in Chlamydiaceae Exploits Differential Tryptophan Contents of the Protein Repertoire

Xie

Bonner

et al. 2012

Microbiol Mol Biol Rev

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SUMMARY One form of immune evasion is a developmental state called “persistence” whereby chlamydial pathogens respond to the host-mediated withdrawal of l -tryptophan (Trp). A sophisticated survival mode of reversible quiescence is implemented. A mechanism has evolved which suppresses gene products necessary for rapid pathogen proliferation but allows expression of gene products that underlie the morphological and developmental characteristics of persistence. This switch from one translational profile to an alternative translational profile of newly synthesized proteins is proposed to be accomplished by maximizing the Trp content of some proteins needed for rapid proliferation (e.g., ADP/ATP translocase, hexose-phosphate transporter, phosphoenolpyruvate [PEP] carboxykinase, the Trp transporter, the Pmp protein superfamily for cell adhesion and antigenic variation, and components of the cell division pathway) while minimizing the Trp content of other proteins supporting the state of persistence. The Trp starvation mechanism is best understood in the human- Chlamydia trachomatis relationship, but the similarity of up-Trp and down-Trp proteomic profiles in all of the pathogenic Chlamydiaceae suggests that Trp availability is an underlying cue relied upon by this family of pathogens to trigger developmental transitions. The biochemically expensive pathogen strategy of selectively increased Trp usage to guide the translational profile can be leveraged significantly with minimal overall Trp usage by (i) regional concentration of Trp residue placements, (ii) amplified Trp content of a single protein that is required for expression or maturation of multiple proteins with low Trp content, and (iii) Achilles'-heel vulnerabilities of complex pathways to high Trp content of one or a few enzymes.

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Genotypic Differences in theChlamydia pneumoniae tyrP Locus Related to Vascular Tropism and Pathogenicity

Cited by 34 publications

References 26 publications

Molecular Mechanism of Tryptophan-Dependent Transcriptional Regulation inChlamydia trachomatis

Molecular Mechanism of Tryptophan-Dependent Transcriptional Regulation inChlamydia trachomatis

Arginine-Dependent Gene Regulation via the ArgR Repressor Is Species Specific inChlamydia

The AlternativeTranslational Profile That Underlies the Immune-Evasive State of Persistence in Chlamydiaceae Exploits Differential Tryptophan Contents of the Protein Repertoire

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