The
            <i>Enterococcus faecalis pyr</i>
            Operon Is Regulated by Autogenous Transcriptional Attenuation at a Single Site in the 5′ Leader

Ghim, Sa‐Youl; Kim, Charles C.; Bonner, Eric R.; D'Elia, John; Grabner, Gail K.; Switzer, Robert L.

doi:10.1128/jb.181.4.1324-1329.1999

Cited by 20 publications

(5 citation statements)

References 19 publications

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“…The significant up-regulation of these genes may promote pyrimidine biosynthetic in the alkaline stress. The capacity for de novo pyrimidine biosynthesis is required for the virulence of some bacteria (Ghim et al, 1999 ).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of Enterococcus faecalis in response to alkaline stress

et al. 2015

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Enterococcus faecalis is the most commonly isolated species from endodontic failure root canals; its persistence in treated root canals has been attributed to its ability to resist high pH stress. The goal of this study was to characterize the E. faecalis transcriptome and to identify candidate genes for response and resistance to alkaline stress using Illumina HiSeq 2000 sequencing. We found that E. faecalis could survive and form biofilms in a pH 10 environment and that alkaline stress had a great impact on the transcription of many genes in the E. faecalis genome. The transcriptome sequencing results revealed that 613 genes were differentially expressed (DEGs) for E. faecalis grown in pH 10 medium; 211 genes were found to be differentially up-regulated and 402 genes differentially down-regulated. Many of the down-regulated genes found are involved in cell energy production and metabolism and carbohydrate and amino acid metabolism, and the up-regulated genes are mostly related to nucleotide transport and metabolism. The results presented here reveal that cultivation of E. faecalis in alkaline stress has a profound impact on its transcriptome. The observed regulation of genes and pathways revealed that E. faecalis reduced its carbohydrate and amino acid metabolism and increased nucleotide synthesis to adapt and grow in alkaline stress. A number of the regulated genes may be useful candidates for the development of new therapeutic approaches for the treatment of E. faecalis infections.

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Section: Discussionmentioning

confidence: 99%

Transcriptome analysis of Enterococcus faecalis in response to alkaline stress

et al. 2015

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“…In both bacteria and mammals,¯ux through the pyrimidinebiosynthesis pathway is feedback-regulated at the ®rst rate-limiting step (negatively by pyrimidine nucleotides and positively by PRPP), but in mammals this involves a complex network of both allosteric and phosphorylation control mechanisms (Sigoillot et al, 2003). In bacteria, the second regulatory mechanism involving autogenous transcriptional termination and antitermination via pyrR is proposed to control expression of the operon (Ghim et al, 1994;Turner et al, 1994;Ghim et al, 1999). Notwithstanding the challenges of modeling or predicting allosteric attenuation of transcription within the operon by virtual screening, the putative regulatory protein pyrR is an attractive target for antitubercular drug development, particularly as differences between mammalian and bacterial pathways are exploited.…”

Section: The Pyr Pathway As a Target For Antitubercular Drugsmentioning

confidence: 99%

“…Because pyrR binding to mRNA is tighter in the presence of UMP or UTP (Tomchick et al, 1998), elevated intracellular levels of these nucleotides act to attenuate transcription, thus reducing expression of downstream pyr genes. PyrR proteins are evolutionarily related to uracil phosphoribosyltransferases (UPRTases), as demonstrated by sequence and structural similarities, and several pyrR proteins have been shown to be bifunctional (Van de Casteele et al, 1997;Turner et al, 1998;Ghim et al, 1999). Bacillus subtilis pyrR, in addition to attenuating transcription at three sites within the operon, has been shown to possess UPRTase activity (Turner et al, 1998), although most of the UPRTase activity and thus uracil salvage in B. subtilis arises from a second UPRTase-encoding gene, upp (Martinussen et al, 1995), which is also present in Mtb.…”

Section: Mechanism Of Pyrr Regulationmentioning

confidence: 99%

Structure of pyrR (Rv1379) fromMycobacterium tuberculosis: a persistence gene and protein drug target

Kantardjieff

Vásquez

Castro

et al. 2005

Acta Crystallogr D Biol Cryst

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The Mycobacterium tuberculosis pyrR gene (Rv1379) encodes a protein that regulates the expression of pyrimidine-nucleotide biosynthesis (pyr) genes in a UMP-dependent manner. Because pyrimidine biosynthesis is an essential step in the progression of TB, the gene product pyrR is an attractive antitubercular drug target. The 1.9 A native structure of Mtb pyrR determined by the TB Structural Genomics Consortium facilities in trigonal space group P3(1)21 is reported, with unit-cell parameters a = 66.64, c = 154.72 A at 120 K and two molecules in the asymmetric unit. The three-dimensional structure and residual uracil phosphoribosyltransferase activity point to a common PRTase ancestor for pyrR. However, while PRPP- and UMP-binding sites have been retained in Mtb pyrR, a distinct dimer interaction among subunits creates a deep positively charged cleft capable of binding pyr mRNA. In silico screening of pyrimidine-nucleoside analogs has revealed a number of potential lead compounds that, if bound to Mtb pyrR, could facilitate transcriptional attenuation, particularly cyclopentenyl nucleosides.

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“…Bacillus subtilis is not the only organism to utilize this form of transcriptional attenuation to regulate its pyr genes. Homologous regulatory systems have been found in Bacillus caldolyticus (7), Enterococcus faecalis (8), Lactobacillus plantarum (9) and Lactococcus lactis (10)(11)(12). It appears from examination of genome sequences that PyrR-dependent regulation of pyr genes is found in many other bacterial species as well (6).…”

Section: Introductionmentioning

confidence: 99%

Molecular recognition of pyr mRNA by the Bacillus subtilis attenuation regulatory protein PyrR

Bonner

D'Elia

Billips

et al. 2001

Nucleic Acids Research

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The pyrimidine nucleotide biosynthesis (pyr) operon in Bacillus subtilis is regulated by transcriptional attenuation. The PyrR protein binds in a uridine nucleotide-dependent manner to three attenuation sites at the 5'-end of pyr mRNA. PyrR binds an RNA-binding loop, allowing a terminator hairpin to form and repressing the downstream genes. The binding of PyrR to defined RNA molecules was characterized by a gel mobility shift assay. Titration indicated that PyrR binds RNA in an equimolar ratio. PyrR bound more tightly to the binding loops from the second (BL2 RNA) and third (BL3 RNA) attenuation sites than to the binding loop from the first (BL1 RNA) attenuation site. PyrR bound BL2 RNA 4-5-fold tighter in the presence of saturating UMP or UDP and 150- fold tighter with saturating UTP, suggesting that UTP is the more important co-regulator. The minimal RNA that bound tightly to PyrR was 28 nt long. Thirty-one structural variants of BL2 RNA were tested for PyrR binding affinity. Two highly conserved regions of the RNA, the terminal loop and top of the upper stem and a purine-rich internal bulge and the base pairs below it, were crucial for tight binding. Conserved elements of RNA secondary structure were also required for tight binding. PyrR protected conserved areas of the binding loop in hydroxyl radical footprinting experiments. PyrR likely recognizes conserved RNA sequences, but only if they are properly positioned in the correct secondary structure.

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The Enterococcus faecalis pyr Operon Is Regulated by Autogenous Transcriptional Attenuation at a Single Site in the 5′ Leader

Cited by 20 publications

References 19 publications

Transcriptome analysis of Enterococcus faecalis in response to alkaline stress

Transcriptome analysis of Enterococcus faecalis in response to alkaline stress

Structure of pyrR (Rv1379) fromMycobacterium tuberculosis: a persistence gene and protein drug target

Molecular recognition of pyr mRNA by the Bacillus subtilis attenuation regulatory protein PyrR

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