Structure of GrlR and the Implication of Its EDED Motif in Mediating the Regulation of Type III Secretion System in EHEC

Jobichen, Chacko; Li, Mo; Yerushalmi, Gal; Tan, Yih Wan; Mok, Yu Keung; Rosenshine, Ilan; Leung, Ka Yin; Sivaraman, J.

doi:10.1371/journal.ppat.0030069

Cited by 30 publications

(35 citation statements)

References 41 publications

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“…Using a yeast two-hybrid system, it was reported earlier that these two proteins interact with each other, although their functions were unknown at the time (12). This interaction has been confirmed experimentally using biochemical techniques (29,33,37). Based on this feature, it has been proposed that GrlR represses LEE gene expression by binding to GrlA, thus preventing its interaction with the ler promoter.…”

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confidence: 77%

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Molecular Characterization of GrlA, a Specific Positive Regulator of ler Expression in Enteropathogenic Escherichia coli

et al. 2010

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Some of these mutants, albeit inactive, were still able to interact with the negative regulator GrlR, indicating that loss of activity was not a consequence of protein misfolding. Additional residues in the vicinity of the HTH domain, as well as at the end of the protein, were also shown to be important for GrlA activity as a transcriptional regulator, but not for its interaction with GrlR. In summary, GrlA consists of at least two functional domains, one involved in transcriptional activation and DNA binding and the other in heterodimerization with GrlR.

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confidence: 77%

“…grlA is cotranscribed with grlR, a gene coding for a negative regulator of LEE gene expression (3,15,29,31,33,40). Using a yeast two-hybrid system, it was reported earlier that these two proteins interact with each other, although their functions were unknown at the time (12).…”

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confidence: 99%

Molecular Characterization of GrlA, a Specific Positive Regulator of ler Expression in Enteropathogenic Escherichia coli

et al. 2010

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“…The grlA gene is positioned downstream of an open reading frame named grlR (encoding GrlR [global regulator of LEE repressor]) within the same transcriptional unit. In contrast to GrlA, the GrlR protein exerts a negative effect on LEE1 expression (1,14,32), by forming heterodimers with GrlA (11,28).…”

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Transcriptional Analysis of the grlRA Virulence Operon from Citrobacter rodentium

et al. 2010

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The locus for enterocyte effacement (LEE) is the virulence hallmark of the attaching-and-effacing (A/E) intestinal pathogens, namely, enteropathogenic Escherichia coli, enterohemorrhagic E. coli, and Citrobacter rodentium. The LEE carries more than 40 genes that are arranged in several operons, e.g., LEE1 to LEE5. Expression of the various transcriptional units is subject to xenogeneic silencing by the histone-like protein H-NS. The LEE1-encoded regulator, Ler, plays a key role in relieving this repression at several major LEE promoters, including LEE2 to LEE5. To achieve appropriate intracellular concentrations of Ler in different environments, A/E pathogens have evolved a sophisticated regulatory network to control ler expression. For example, the LEE-encoded GrlA and GrlR proteins work as activator and antiactivator, respectively, of ler transcription. Thus, control of the transcriptional activities of the LEE1 (ler) promoter and the grlRA operon determines the rate of transcription of all of the LEE-encoded virulence factors. To date, only a single promoter has been identified for the grlRA operon. In this study, we showed that the non-LEE-encoded AraC-like regulatory protein RegA of C. rodentium directly stimulates transcription of the grlRA promoter by binding to an upstream region in the presence of bicarbonate ions. In addition, in vivo and in vitro transcription assays revealed a 70 promoter that is specifically responsible for transcription of grlA. Expression from this promoter was strongly repressed by H-NS and its paralog StpA but was activated by Ler. DNase I footprinting demonstrated that Ler binds to a region upstream of the grlA promoter, whereas H-NS interacts specifically with a region extending from the grlA core promoter into its coding sequence. Together, these findings provide new insights into the environmental regulation and differential expressions of the grlR and grlA genes of C. rodentium.Citrobacter rodentium causes transmissible colonic hyperplasia and diarrhea in mice (34). Like the human diarrheagenic pathogens enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC), C. rodentium induces attaching-and-effacing (A/E) lesions in the intestinal epithelium of its host (40, 49). All three of these enteric pathogens possess a pathogenicity island known as the locus for enterocyte effacement (LEE), which is responsible for the A/E phenotype (13,18,27,36,43). So far, all of the LEE-encoded virulence factors investigated in C. rodentium play roles in virulence equivalent to the roles played by those from EPEC and EHEC (14). Furthermore, the regulatory networks controlling transcription of the LEE are broadly similar in the three pathogens (37, 63). For these reasons, infection of mice with C. rodentium has been used as a convenient small animal model to investigate the molecular and cellular pathogenesis of EPEC and EHEC and the regulation of LEE expression by these organisms (14,40).The LEE comprises 41 open reading frames, most of which are clustered into five opero...

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“…The strains were cultured under conditions known to stimulate LEE gene expression and then assayed for light production. Under these growth conditions, the grlR mutant exhibited a slower growth rate than the other strains for unknown reasons, although the absence of GrlR may allow for unregulated GrlA activity (higher LEE gene transcriptional activation; Jiménez et al, 2010;Jobichen et al, 2007). All the strains produced light at levels near to those of wild-type , EHEC isolates (middle) and C. rodentium (bottom).…”

Section: Known Lee Transcriptional Regulators Are Not Required For Cementioning

confidence: 99%

“…GrlA is a transcriptional activator with a helix-turnhelix motif, binding to DNA near promoter elements (Jimenéz et al, 2010). GrlR is known to interact with GrlA and prevent GrlA binding to DNA, thereby acting as an inhibitor of GrlA function (Jobichen et al, 2007). The GrlA and GrlR proteins thus impose another level of regulatory control.…”

Section: Introductionmentioning

confidence: 99%

Dual temporal transcription activation mechanisms control cesT expression in enteropathogenic Escherichia coli

Brouwers

Thomas

2012

Microbiology

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Structure of GrlR and the Implication of Its EDED Motif in Mediating the Regulation of Type III Secretion System in EHEC

Cited by 30 publications

References 41 publications

Molecular Characterization of GrlA, a Specific Positive Regulator of ler Expression in Enteropathogenic Escherichia coli

Molecular Characterization of GrlA, a Specific Positive Regulator of ler Expression in Enteropathogenic Escherichia coli

Transcriptional Analysis of the grlRA Virulence Operon from Citrobacter rodentium

Dual temporal transcription activation mechanisms control cesT expression in enteropathogenic Escherichia coli

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