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Query: UNIPROT:P06889 (Mol)
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ANR, an analogue of Escherichia coli FNR, has been shown to be necessary for denitrification, arginine deiminase activity and cyanide production of Pseudomonas aeruginosa. Another CRP/FNR-related regulator, DNR, has also been shown to be necessary for denitrification. In this study, we have found that the transcription of the dnr gene is under the control of ANR. When the dnr gene was expressed by tac promoter in an anr mutant, the strain recovered the ability to grow under anaerobic conditions by denitrification. Nitrate, nitrite, nitric oxide and nitrous oxide reducing activities were expressed, and the structural genes for nitrite and nitric oxide reductases were transcribed under anaerobic conditions in the anr mutant strain transformed with the dnr gene. These findings suggest that the expression of the denitrification system is controlled not directly by ANR but indirectly via DNR. The arginine deiminase activity and cyanide production were not regulated by DNR.
Mol Microbiol 1997 Sep
PMID:Cascade regulation of the two CRP/FNR-related transcriptional regulators (ANR and DNR) and the denitrification enzymes in Pseudomonas aeruginosa. 935 Aug 69

An early process in the pathogenesis of enteric bacteria is colonization of the intestinal epithelium leading to local multiplication, pathophysiological interactions with the host and further spreading. Attachment is typically mediated by bacterial fimbriae, which are selectively expressed during growth in the intestine. Here we report an analysis of the regulation of 987P fimbrial expression of enterotoxigenic Escherichia coli (ETEC). Expression of both fasH, the transcriptional activator of the 987P fimbrial genes, and fasA, the major fimbrial subunit, is regulated in response to a variety of environmental stimuli. We have found that expression of fasH is regulated in response to the carbon status of the growth medium by the cAMP-CRP complex. Moreover, fasH is regulated in response to both the nitrogen status of the growth medium and the external pH. Expression of fasA is activated by FasH, and is also selectively regulated in response to growth temperature by HNS. Regulation of fimbrial expression by carbon and/or nitrogen gradients is proposed to provide a mechanism that allows preferential colonization of different segments of the intestine by various enteropathogens, such as ETEC, enteropathogenic E. coli and Vibrio cholerae.
Mol Microbiol 1997 Aug
PMID:Differential regulation of fasA and fasH expression of Escherichia coli 987P fimbriae by environmental cues. 937 7

The Escherichia coli CytR regulator belongs to the LacI family of sequence-specific DNA-binding proteins and prevents CRP-mediated transcription in the CytR regulon. Unlike the other members of this protein family, CytR binds with only modest affinity to its operators and transcription repression thus relies on the formation of nucleoprotein complexes with the cAMP-CRP complex. Moreover, CytR exhibits a rotational and translational flexibility in operator binding that is unprecedented in the LacI family. In this report we examined the effect of changing the spacing between CytR half-operators on CytR regulation in vivo and on CytR binding in vitro. Maximum repression was seen with the short spacing variants: repression peaks when the half-operators lie on the same face of the DNA helix. Repression was retained for most spacing variants with centre separations of half-operators < or = 3 helical turns. Our data confirm and extend the view that CytR is a highly flexible DNA binder that can adapt many different conformations for co-operative binding with CRP. Furthermore, limited proteolysis of radiolabelled CytR protein showed that the interdomain linker connecting the DNA binding domains and the core part of CytR does not become structured upon DNA binding. We conclude that CytR does not use hinge alpha-helices for minor groove recognition. Rather, CytR possesses a highly flexible interdomain linker that allows it to form complexes with CRP at promoters with quite different architecture.
Mol Microbiol 1998 Jan
PMID:DNA-binding characteristics of the Escherichia coli CytR regulator: a relaxed spacing requirement between operator half-sites is provided by a flexible, unstructured interdomain linker. 946 54

The general stress-induced sigma subunit sigma s of Escherichia coli RNA polymerase is closely related to the vegetative sigma factor sigma 70. In view of their very similar promoter specificity in vitro, it is unclear how sigma factor selectivity in the expression of sigma s-dependent genes is generated in vivo. The csiD gene is such a strongly sigma s-dependent gene. In contrast to sigma s, which is induced in response to many different stresses, csiD, whose expression is driven from a single promoter, is induced by carbon starvation only. To our knowledge, the csiD promoter is the first characterized promoter which is not only exclusively dependent on sigma s-containing RNA polymerase (E sigma s), but also requires an activator, cAMP-CRP. In addition, leucine-responsive regulatory protein (Lrp) acts as a positive modulator of csiD expression. Also in vitro, E sigma s is more efficient than E sigma 70 in csiD promoter binding, open complex formation and run-off transcription, which might be due to the poor match of the csiD -35 region to the sigma 70 consensus and to transcription by E sigma s being less dependent on contacts in this region. By DNase I protection experiments, a cAMP-CRP binding site centered at -68.5 nucleotides upstream of the csiD transcriptional start site was identified. While cAMP-CRP stimulates E sigma 70 binding, it does not promote open complex formation by E sigma 70, but does so in conjunction with E sigma s. With linear templates, cAMP-CRP significantly stimulates E sigma s-mediated in vitro transcription, whereas transcription by E sigma 70 is negligible and hardly stimulated by cAMP-CRP. These findings may reflect different or less stringent positional requirements for an activator site for E sigma s than for E sigma 70, and indicate that cAMP-CRP contributes to sigma factor selectivity at the csiD promoter. In vitro transcription experiments with super-coiled templates, however, revealed significant cAMP-CRP-stimulated transcription also by E sigma 70. Yet, under these conditions, H-NS was found to restore E sigma s specificity by strongly interfering with cAMP-CRP/E sigma 70-dependent transcription. Lrp strongly and cooperatively binds to multiple sites located between positions -14 and -102 (in a way that suggests DNA wrapping around multiple Lrp molecules) and moderately stimulates in vitro transcription, especially with E sigma s. In summary, we conclude that the csiD promoter has an intrinsic preference for E sigma s, but that also protein factors such as cAMP-CRP, Lrp and probably H-NS as well as DNA conformation contribute to its strong E sigma s selectivity. Furthermore, this strong E sigma s preference in combination with a requirement for high concentrations of the essential activator cAMP-CRP ensures csiD expression under conditions of carbon starvation, but not other stress conditions.
J Mol Biol 1998 Feb 20
PMID:Molecular analysis of the regulation of csiD, a carbon starvation-inducible gene in Escherichia coli that is exclusively dependent on sigma s and requires activation by cAMP-CRP. 951 7

A Monte Carlo simulation method for studying DNA cyclization (or ring-closure) has been extended to the case of protein-induced bending, and its application to experimental data has been demonstrated. Estimates for the geometric parameters describing the DNA bend induced by the catabolite activator protein (CAP or CRP) were obtained which correctly predict experimental DNA cyclization probabilities (J factors), determined for a set of 11 150 to 166 bp DNA restriction fragments bearing A tracts phased against CAP binding sites. We find that simulation of out-of-phase molecules is difficult and time consuming, requiring the geometric parameters to be optimized individually rather than globally. A wedge angle model for DNA bending was found to make reasonable predictions for the free DNA. The bend angle in the CAP-DNA complex is estimated to be 85 to 90 degrees, in agreement with estimates from gel electrophoresis and X-ray co-crystal structures. Since the DNA is found to have a pre-existing bend of 15 degrees, the change in bend angle induced by CAP is 70 to 75 degrees, in a agreement with an estimate from topological measurements. We find evidence for slight (approximately 10 degrees) unwinding by CAP. The persistence length and helical repeat of the unbound portion of the DNA are in accord with literature-cited values, but the best-fit DNA torsional modulus C is found to be 1.7 (+/- 0.2) x 10(-19) erg. cm, versus literature estimates and best-fit values for the free DNA of 2.0 x 10(-19) to 3.4 x 10(-19) erg.com. Simulations using this low value of C predict that cyclization of molecules with out-of-phase bends proceeds via undertwisting or overtwisting of the DNA between the bends, so as to align the bends, rather than through conformations with substantial writhe. We present experiments on the topoisomers formed by cyclization with CAP which support this conclusion, and thereby rationalize the surprising result that cyclization can actually be enhanced by out-of-phase bends if the twist required to align the bends improves the torsional alignment of the ends. The relationship between the present work and previous studies on DNA bending by CAP is discussed, and recommendations are given for the efficient application of the cyclization/simulation approach to DNA bending.
J Mol Biol 1998 Feb 13
PMID:Measurement of the DNA bend angle induced by the catabolite activator protein using Monte Carlo simulation of cyclization kinetics. 951 24

HIV-1-infected patients are in chronic oxidative stress and clastogenic factors (CFs) are present in their plasma. CFs from patients with HIV are formed via superoxide anion radical and stimulate further superoxide production. The pathophysiolgic significance and the exact composition of the circulating clastogenic material in patients with HIV is unknown. Cytokines, such as tumor necrosis factor-alpha (TNF-alpha), are increased in the plasma of patients with HIV and TNF-alpha shows clastogenic activity in vitro. The aim of this clinical study was to compare levels of CF in HIV-1-positive patients with asymptomatic disease, opportunistic infections, and malignancies with those in HIV-1-negative control groups and to correlate CF activity with CD4+ T cell numbers, the cytokines (TNF-alpha, interleukin-2 [IL-2], IL-6), and the inflammatory markers (C-reactive protein [CRP], neopterin, granulocyte elastase). CFs were significantly increased in all HIV-1-positive patients and in HIV-1-negative patients with malignant tumors. HIV-1-positive patients with Kaposi's sarcoma showed the highest CF activity in their plasma (p < 0.08). CFs appear very early in HIV infection, and they correlate negatively with CD4+ T cells, which are an indicator of disease activity. The presence of CF in the plasma of HIV-infected patients is not a general response to a viral infection because these factors are not increased in HIV-1-negative patients with viral infection (zoster). CFs are not specific for the HIV-1 infection; they also occur in HIV-1-negative patients with malignant tumors. There was a tendency towards a positive correlation (p < 0.14) between CF and TNF-alpha but there was no positive correlation of CF with IL-2, IL-6, CRP, elastase, and neopterin levels. This indicates that TNF-alpha may be among the components of CF in HIV-1-infected patients. In addition, other unidentified components may contribute to the clastogenic activity of the plasma or the composition of CF may vary from patient to patient. Further clinical studies with larger sample populations are necessary to analyze the composition of CF in HIV-1-positive patients.
Mol Med 1998 May
PMID:Multiparameter analysis of clastogenic factors, pro-oxidant cytokines, and inflammatory markers in HIV-1-infected patients with asymptomatic disease, opportunistic infections, and malignancies. 964 83

We have shown previously that the dadAX operon of Escherichia coli expresses multiple transcripts, which are repressed by leucine-responsive regulatory protein (Lrp). Here we used site-directed mutagenesis and in vitro and in vivo transcription assays to show that each of the three major dad transcripts requires a specific promoter. These promoters, P1-P3, overlap and are positively regulated in vivo by cyclic AMP-CRP. DNase I footprinting experiments localized two CRP binding sites in this region: CRP1, which is positioned upstream of P1-P3, and CRP2, which is located within the promoters. Site-directed mutagenesis of each site provided evidence that CRP1 is necessary for the effects of cyclic AMP-CRP on dad expression in vivo and in vitro, and that CRP2 probably plays little or no role in this process.
Mol Gen Genet 1998 May
PMID:In vitro and in vivo characterization of three major dadAX promoters in Escherichia coli that are regulated by cyclic AMP-CRP and Lrp. 964 52

A phosphorylcholine-reactive protein was isolated from serum of Atlantic salmon (Salmo salar L.) by affinity chromatography on a phosphorylcholine-conjugated Sepharose column followed by elution with phosphorylcholine. Based on the method used we describe the isolated protein as salmon phosphorylcholine-reactive protein (salmon PRP). Salmon PRP has calcium-independent binding to phosphorylcholine. The protein exists in a monomeric and dimeric form with molecular weight of approximately 80 and 160 kD, respectively. Separation of the protein preparation on SDS-PAGE under reducing conditions resulted in disappearance of the 80 and 160 kD bands and appearance of a major protein band of approximately 100 kD. The N-terminal amino acid sequences of the non-reduced 80 and 160 kD bands and the reduced 100 kD band were identical. Apart from the dimeric form, the molecular weight of salmon PRP and its appearance on SDS-PAGE is similar to human plasminogen. Comparison of the sequence in a protein database resulted in approximately 50% identity with human and bovine plasminogen. In addition, cross-reactivity between antibodies to human plasminogen and salmon PRP was demonstrated. Thus, salmon PRP appears to be different from other phosphorylcholine-reactive proteins which are mostly reported to be CRP-like proteins with calcium-dependent binding to phosphorylcholine, pentameric ring-structure and sequence homology between species. Whether salmon PRP is a new type of phosphorylcholine-binding protein with an unknown function or a plasminogen-like protein with binding specificity for phosphorylcholine calls for further investigation.
Comp Biochem Physiol B Biochem Mol Biol 1998 Mar
PMID:Atypical phosphorylcholine-reactive protein from Atlantic salmon, Salmo salar L. 973 31

In Escherichia coli, the rpoH gene encoding the essential heat-shock regulator sigma32, is expressed in a complex manner. Transcription occurs from four promoters (P1, P3, P4 and P5) and is modulated by several factors including (i) two sigma factors (sigma70 and sigmaE); (ii) the global regulator CRP; and (iii) the DnaA protein. Here, a further dissection of the rpoH regulatory region has revealed that an additional transcription control exists that appears to link rpoH expression to nucleoside metabolism. The cAMP-CRP complex and the CytR anti-activator bind co-operatively to the promoter region forming a repression complex that overlaps the sigmaE-dependent P3 promoter and the sigma70-dependent P4 and P5 promoters. During steady-state growth conditions with glycerol as the carbon and energy source, transcription from P3, P4 and P5 is reduced approximately threefold by CytR, whereas transcription from the upstream promoter, P1, appears to be unaffected. Furthermore, in strains that slightly overproduce CytR, transcription from P3, P4 and P5 is reduced even further (approximately 10-fold), and repression can be fully neutralized by the addition of the inducer cytidine to the growth medium. In the induced state, P4 is the strongest promoter and, together with P3 and P5, it is responsible for most rpoH transcription (65-70%). At present, CytR has been shown to 'fine tune' transcription of two genes (rpoH and ppiA) that are connected with protein-folding activities. These findings suggest that additional assistance in protein folding is required under conditions in which CytR is induced (i.e. in the presence of nucleosides).
Mol Microbiol 1998 Aug
PMID:Transcription of rpoH, encoding the Escherichia coli heat-shock regulator sigma32, is negatively controlled by the cAMP-CRP/CytR nucleoprotein complex. 998 39

The expI-expR locus drives a quorum-sensing system in the phytopathogenic bacterium, Erwinia chrysanthemi. Purified ExpR, an N-acyl homoserine lactone-responsive regulatory protein, binds to the promoter/operator region of the expI and expR genes. DNase I footprinting experiments showed that ExpR protects the regions between -66 and -40 from the P1 transcription initiation site of expl and between -54 and -18 from the expR transcription initiation site P1. The protected region overlaps the two expR promoters, P1 and P2, suggesting that ExpR exerts a negative control on its own gene expression. This assertion is reinforced by the fact that the addition of OHHL dissociates the ExpR-expR DNA complex. In contrast, the location of the ExpR binding site on the expI gene suggests an activator function, as reported for the pel genes. Moreover, ExpR is able to induce DNA bending. In vivo and in vitro studies revealed that CRP functions as an activator of expR expression, but as a repressor of expI transcription. A second level of control of expR and expI occurs through the PecS repressor, a regulator of pectinase synthesis. PecS represses expI expression, while ExpR activates pecS transcription, suggesting the existence of a mutual control between pecS and the expI-expR system in E. chrysanthemi. Regulation of pectinase synthesis in soft rot Erwinia appears to be a complex network of multiple cross-acting regulatory elements. A model that integrates these regulatory elements is proposed.
Mol Microbiol 1998 Sep
PMID:Integration of the quorum-sensing system in the regulatory networks controlling virulence factor synthesis in Erwinia chrysanthemi. 978 78


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