LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 1941

Search options

  1. Article ; Online: Selective Hydroxylation of C(sp

    Abas, Hossay / Blencowe, Peter / Brookfield, Joanna L / Harwood, Lucy A

    Chemistry (Weinheim an der Bergstrasse, Germany)

    2023  Volume 29, Issue 44, Page(s) e202301066

    Abstract: ... of oxidation being key to their biological activity and physicochemical properties. These C(sp ...

    Abstract Steroids are highly prevalent structures in small-molecule therapeutics, with the level of oxidation being key to their biological activity and physicochemical properties. These C(sp
    MeSH term(s) Hydroxylation ; Oxidation-Reduction ; Oxidants/chemistry ; Steroids/metabolism ; Biocatalysis
    Chemical Substances Oxidants ; Steroids
    Language English
    Publishing date 2023-07-12
    Publishing country Germany
    Document type Journal Article ; Review
    ZDB-ID 1478547-X
    ISSN 1521-3765 ; 0947-6539
    ISSN (online) 1521-3765
    ISSN 0947-6539
    DOI 10.1002/chem.202301066
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  2. Article ; Online: C-arm contamination of the surgical field: Can contamination be reduced with an intervening drape?

    Magee, Lacey C / Piazza, Brian / Harwood, Kathleen / Lawrence, J Todd R

    Injury

    2022  Volume 53, Issue 6, Page(s) 1994–1998

    Abstract: Introduction: Contamination of the surgical field by the C-arm in orthopaedic procedures is ... the utility of a split sheet to aid in prevention of secondary contamination from the C-arm on the C-arm side ... of the operative field.: Methods: A C-arm and a surgical table were draped by standard techniques. The surgical ...

    Abstract Introduction: Contamination of the surgical field by the C-arm in orthopaedic procedures is a significant potential source for surgical site infections. The purpose of this study was to explore the utility of a split sheet to aid in prevention of secondary contamination from the C-arm on the C-arm side of the operative field.
    Methods: A C-arm and a surgical table were draped by standard techniques. The surgical table was split in thirds: the surgeon's side, the C-arm side of the operative field, and the middle for contamination analysis. Fluorescent powder was used to simulate a contaminant and placed on the C-arm, floor and lower portions of drapes. The C-arm was cycled between PA and Lateral positions. Powder transfer to the field was visualized with a camera under uniform UV light. Photographs were taken to measure fluorescent pixels prior to cycling the C-arm and at 5, 10 and 15 cycles. This protocol was repeated using a split sheet (U-drape) to isolate the C-arm below the operative field. Image J was utilized to calculate differences in the number of pixels brighter than the control image.
    Results: Using standard draping techniques, there was contamination of the surgical field with the C-arm side of the operative field having the highest level of fluorescent pixels. The number of fluorescent pixels was linearly correlated with the number of PA to Lateral cycles. At the end of 15 cycles, the average number of fluorescent pixels for the intervening draping technique was 2.9 pixels compared to the standard draping technique of 3939 pixels (p = 0.0078).
    Discussion: The addition of a U-drape between the C-arm and the table results in a statistically significant reduction in surgical field contamination as a result of secondary transfer from the C-arm.
    Level of evidence: II.
    MeSH term(s) Humans ; Orthopedic Procedures ; Powders ; Surgical Equipment ; Surgical Wound Infection/prevention & control
    Chemical Substances Powders
    Language English
    Publishing date 2022-03-26
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 218778-4
    ISSN 1879-0267 ; 0020-1383
    ISSN (online) 1879-0267
    ISSN 0020-1383
    DOI 10.1016/j.injury.2022.03.046
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  3. Article ; Online: Volunteering for Infection: Participant Perspectives on a Hepatitis C Virus Controlled Human Infection Model.

    Eberts, Jake D / Zimmer-Harwood, Paul / Elsey, James W B / Fraser-Urquhart, Alastair / Smiley, Thomas

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

    2023  Volume 77, Issue Suppl 3, Page(s) S224–S230

    Abstract: ... bolstered by a survey of 117 potential hepatitis C virus CHIM participants, we present ideas to inform ...

    Abstract Ethical human subjects research requires participants to be treated safely and respectfully, yet much bioethical debate takes place without participants. We aim to address this gap in the context of controlled human infection model (CHIM) research. Based upon our own experience as study participants, and bolstered by a survey of 117 potential hepatitis C virus CHIM participants, we present ideas to inform efficient, ethical, and scientifically useful study design. We advocate for full protocol transparency, higher compensation, commitment to the rapid dissemination of study results, and proactive efforts to detail risk-minimization efforts as early as possible in the recruitment process, among other measures. We encourage researchers to proactively partner with volunteer advocacy organizations that promote collective representation of volunteers to maximize their agency, and guard against ethical issues arising from healthy human subjects research.
    MeSH term(s) Humans ; Hepacivirus ; Volunteers ; Research Design
    Language English
    Publishing date 2023-08-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1099781-7
    ISSN 1537-6591 ; 1058-4838
    ISSN (online) 1537-6591
    ISSN 1058-4838
    DOI 10.1093/cid/ciad350
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  4. Article ; Online: Mechanistic insights into c-di-GMP-dependent control of the biofilm regulator FleQ from Pseudomonas aeruginosa.

    Matsuyama, Bruno Y / Krasteva, Petya V / Baraquet, Claudine / Harwood, Caroline S / Sondermann, Holger / Navarro, Marcos V A S

    Proceedings of the National Academy of Sciences of the United States of America

    2016  Volume 113, Issue 2, Page(s) E209–18

    Abstract: ... sessile biofilms represents a regulated process orchestrated by the intracellular second-messenger c-di ... GMP. A main effector for c-di-GMP signaling in the opportunistic pathogen Pseudomonas aeruginosa is ... 54)-interaction domain, flanked by a C-terminal helix-turn-helix DNA-binding motif and a divergent N ...

    Abstract Bacterial biofilm formation during chronic infections confers increased fitness, antibiotic tolerance, and cytotoxicity. In many pathogens, the transition from a planktonic lifestyle to collaborative, sessile biofilms represents a regulated process orchestrated by the intracellular second-messenger c-di-GMP. A main effector for c-di-GMP signaling in the opportunistic pathogen Pseudomonas aeruginosa is the transcription regulator FleQ. FleQ is a bacterial enhancer-binding protein (bEBP) with a central AAA+ ATPase σ(54)-interaction domain, flanked by a C-terminal helix-turn-helix DNA-binding motif and a divergent N-terminal receiver domain. Together with a second ATPase, FleN, FleQ regulates the expression of flagellar and exopolysaccharide biosynthesis genes in response to cellular c-di-GMP. Here we report structural and functional data that reveal an unexpected mode of c-di-GMP recognition that is associated with major conformational rearrangements in FleQ. Crystal structures of FleQ's AAA+ ATPase domain in its apo-state or bound to ADP or ATP-γ-S show conformations reminiscent of the activated ring-shaped assemblies of other bEBPs. As revealed by the structure of c-di-GMP-complexed FleQ, the second messenger interacts with the AAA+ ATPase domain at a site distinct from the ATP binding pocket. c-di-GMP interaction leads to active site obstruction, hexameric ring destabilization, and discrete quaternary structure transitions. Solution and cell-based studies confirm coupling of the ATPase active site and c-di-GMP binding, as well as the functional significance of crystallographic interprotomer interfaces. Taken together, our data offer unprecedented insight into conserved regulatory mechanisms of gene expression under direct c-di-GMP control via FleQ and FleQ-like bEBPs.
    MeSH term(s) Amino Acid Motifs ; Amino Acid Sequence ; Bacterial Proteins/chemistry ; Bacterial Proteins/metabolism ; Base Sequence ; Binding Sites ; Biofilms/drug effects ; Calorimetry ; Conserved Sequence ; Cross-Linking Reagents ; Crystallography, X-Ray ; Cyclic GMP/analogs & derivatives ; Cyclic GMP/pharmacology ; DNA, Bacterial/metabolism ; Gene Expression Regulation, Bacterial/drug effects ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Mutant Proteins/chemistry ; Promoter Regions, Genetic/genetics ; Protein Multimerization/drug effects ; Protein Stability ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Pseudomonas aeruginosa/drug effects ; Pseudomonas aeruginosa/genetics ; Pseudomonas aeruginosa/physiology ; Sequence Alignment ; Solutions ; Temperature ; Trans-Activators/chemistry ; Trans-Activators/metabolism ; Transcription, Genetic
    Chemical Substances Bacterial Proteins ; Cross-Linking Reagents ; DNA, Bacterial ; FleQ protein, Pseudomonas aeruginosa ; Mutant Proteins ; Solutions ; Trans-Activators ; bis(3',5')-cyclic diguanylic acid (61093-23-0) ; Cyclic GMP (H2D2X058MU)
    Language English
    Publishing date 2016-01-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1523148113
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  5. Article ; Online: Dietary sodium restriction sex specifically impairs endothelial function via mineralocorticoid receptor-dependent reduction in NO bioavailability in Balb/C mice.

    Faulkner, Jessica L / Harwood, Daisy / Kennard, Simone / Antonova, Galina / Clere, Nicolas / Belin de Chantemèle, Eric J

    American journal of physiology. Heart and circulatory physiology

    2020  Volume 320, Issue 1, Page(s) H211–H220

    Abstract: ... impairs endothelial function in otherwise healthy female mice. We fed male and female Balb/C mice a normal ...

    Abstract Recent findings from our group demonstrated that females exhibit higher endothelial mineralocorticoid receptor (MR) expression than males, which predisposes them to aldosterone-mediated endothelial dysfunction in the context of metabolic disorders. However, whether the endothelium of female mice presents a higher propensity to MR-mediated dysfunction than that of males in the absence of comorbidities remains unknown. We therefore sought to investigate whether increasing aldosterone production endogenously with sodium restriction impairs endothelial function in otherwise healthy female mice. We fed male and female Balb/C mice a normal (0.4% NaCl; NSD) or sodium-restricted diet (0.05% NaCl; SRD) for 4 wk. Females exhibited higher baseline endothelial function (relaxation to acetylcholine) and lower vascular contractility (constriction to phenylephrine, serotonin, and KCl). However, SRD impaired endothelial-dependent relaxation and increased vascular contractility in female mice, effectively ablating the baseline sex difference. Female sex also increased baseline adrenal
    MeSH term(s) Adrenal Glands/enzymology ; Aldosterone/blood ; Animals ; Cytochrome P-450 CYP11B2/metabolism ; Diet, Sodium-Restricted ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/physiopathology ; Female ; Male ; Mice, Inbred BALB C ; NADPH Oxidase 4/metabolism ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type III/metabolism ; Receptor, Angiotensin, Type 1/metabolism ; Receptors, Mineralocorticoid/metabolism ; Sex Factors ; Signal Transduction ; Up-Regulation ; Vasoconstriction ; Vasodilation ; Mice
    Chemical Substances Receptor, Angiotensin, Type 1 ; Receptors, Mineralocorticoid ; Nitric Oxide (31C4KY9ESH) ; Aldosterone (4964P6T9RB) ; Nitric Oxide Synthase Type III (EC 1.14.13.39) ; Nos3 protein, mouse (EC 1.14.13.39) ; Cytochrome P-450 CYP11B2 (EC 1.14.15.4) ; NADPH Oxidase 4 (EC 1.6.3.-) ; Nox4 protein, mouse (EC 1.6.3.-)
    Language English
    Publishing date 2020-10-23
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 603838-4
    ISSN 1522-1539 ; 0363-6135
    ISSN (online) 1522-1539
    ISSN 0363-6135
    DOI 10.1152/ajpheart.00413.2020
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  6. Article ; Online: Use of Nonradiochemical DNAse Footprinting to Analyze c-di-GMP Modulation of DNA-Binding Proteins.

    Baraquet, Claudine / Harwood, Caroline S

    Methods in molecular biology (Clifton, N.J.)

    2017  Volume 1657, Page(s) 303–315

    Abstract: ... lifestyle is a regulated process orchestrated by the intracellular second-messenger c-di-GMP (bis-(3'-5' ... cyclic dimeric guanosine monophosphate). To modulate this transition, c-di-GMP acts ... of how a transcriptional regulator modulates gene expression in response to c-di-GMP binding. DNase ...

    Abstract The transition of bacteria from a planktonic lifestyle to a collaborative, sessile biofilm lifestyle is a regulated process orchestrated by the intracellular second-messenger c-di-GMP (bis-(3'-5')-cyclic dimeric guanosine monophosphate). To modulate this transition, c-di-GMP acts at the transcriptional, posttranscriptional, and posttranslational levels. In this chapter, we describe a method to study of how a transcriptional regulator modulates gene expression in response to c-di-GMP binding. DNase I footprinting is a valuable tool for use in analyzing how regulatory proteins bind to DNA, the location of their binding sites or how c-di-GMP affects their binding to DNA. This chapter describes a protocol for nonradiochemical DNase I footprinting experiments using a capillary electrophoresis method based on the interaction of the Pseudomonas aeruginosa FleQ protein with the promoter regions of biofilm-related genes.
    MeSH term(s) Binding Sites ; Cyclic GMP/analogs & derivatives ; Cyclic GMP/metabolism ; DNA Footprinting/methods ; DNA, Bacterial ; DNA-Binding Proteins/metabolism ; Deoxyribonuclease I/metabolism ; Electrophoresis, Capillary/methods ; Fluorescent Dyes ; Promoter Regions, Genetic ; Staining and Labeling ; Transcription Factors/metabolism
    Chemical Substances DNA, Bacterial ; DNA-Binding Proteins ; Fluorescent Dyes ; Transcription Factors ; bis(3',5')-cyclic diguanylic acid (61093-23-0) ; Deoxyribonuclease I (EC 3.1.21.1) ; Cyclic GMP (H2D2X058MU)
    Language English
    Publishing date 2017
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-4939-7240-1_24
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  7. Article ; Online: Lack of Suppression of Aldosterone Production Leads to Salt-Sensitive Hypertension in Female but Not Male Balb/C Mice.

    Faulkner, Jessica L / Harwood, Daisy / Bender, Lily / Shrestha, Lenee / Brands, Michael W / Morwitzer, M Jane / Kennard, Simone / Antonova, Galina / Belin de Chantemèle, Eric J

    Hypertension (Dallas, Tex. : 1979)

    2018  Volume 72, Issue 6, Page(s) 1397–1406

    Abstract: ... therefore, elucidation of these mechanisms in female animal models is needed. We have previously shown that female Balb/C ... that female Balb/C mice develop salt-sensitive increases in blood pressure. Seven-day feeding of a 4% NaCl ... blood pressure and endothelial function in females on an HS diet. Collectively, these data indicate that Balb/C ...

    Abstract Clinical studies indicate that salt-sensitive hypertension is more prevalent in women than in men. However, animal models of salt sensitivity have primarily focused on the mechanisms of salt sensitivity in male animals; therefore, elucidation of these mechanisms in female animal models is needed. We have previously shown that female Balb/C mice have higher aldosterone synthase expression and aldosterone production than males. We hypothesized that female Balb/C mice develop salt-sensitive increases in blood pressure. Seven-day feeding of a 4% NaCl high-salt (HS) diet increased blood pressure in female mice without altering blood pressure in males. Females on an HS diet displayed no apparent increases in sodium retention as assessed by 24-hour urine collection, sodium balance measure, and saline loading excretion analysis. Females on an HS diet exhibited lower renin-angiotensin system activity (plasma Ang II [angiotensin II], plasma renin activity, and ACE [angiotensin-converting enzyme] activity) compared with males but developed a salt-induced elevation in adrenal aldosterone synthase expression and retained higher aldosterone levels than males on HS. This resulted in a higher aldosterone/plasma renin activity ratio in females compared with males on HS feeding. Adrenal mRNA expression of angiotensinogen and leptin receptor was increased in female mice on an HS diet. HS impaired endothelium-dependent relaxation in female mice only. MR (mineralocorticoid receptor) inhibition (eplerenone) restored blood pressure and endothelial function in females on an HS diet. Collectively, these data indicate that Balb/C mice develop sex-discrepant salt-sensitive hypertension likely via aldosterone-MR-mediated mechanisms involving impaired endothelium-dependent relaxation in females only. This study presents the first model of spontaneous sex-specific salt sensitivity, which mimics the human pathology.
    MeSH term(s) Adrenal Glands/metabolism ; Aldosterone/metabolism ; Angiotensinogen/metabolism ; Animals ; Blood Pressure/physiology ; Female ; Hypertension/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Receptors, Leptin/metabolism ; Renin-Angiotensin System/physiology ; Sex Factors ; Sodium Chloride, Dietary
    Chemical Substances Receptors, Leptin ; Sodium Chloride, Dietary ; Angiotensinogen (11002-13-4) ; Aldosterone (4964P6T9RB)
    Language English
    Publishing date 2018-11-26
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 423736-5
    ISSN 1524-4563 ; 0194-911X ; 0362-4323
    ISSN (online) 1524-4563
    ISSN 0194-911X ; 0362-4323
    DOI 10.1161/HYPERTENSIONAHA.118.11303
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  8. Article ; Online: Acute Toxicities of the Saxitoxin Congeners Gonyautoxin 5, Gonyautoxin 6, Decarbamoyl Gonyautoxin 2&3, Decarbamoyl Neosaxitoxin, C-1&2 and C-3&4 to Mice by Various Routes of Administration.

    Selwood, Andrew I / Waugh, Craig / Harwood, David T / Rhodes, Lesley L / Reeve, John / Sim, Jim / Munday, Rex

    Toxins

    2017  Volume 9, Issue 2

    Abstract: Paralytic shellfish poisoning results from consumption of seafood naturally contaminated by saxitoxin and its congeners, the paralytic shellfish toxins (PSTs). The levels of such toxins are regulated internationally, and maximum permitted concentrations ... ...

    Abstract Paralytic shellfish poisoning results from consumption of seafood naturally contaminated by saxitoxin and its congeners, the paralytic shellfish toxins (PSTs). The levels of such toxins are regulated internationally, and maximum permitted concentrations in seafood have been established in many countries. A mouse bioassay is an approved method for estimating the levels of PSTs in seafood, but this is now being superseded in many countries by instrumental methods of analysis. Such analyses provide data on the levels of many PSTs in seafood, but for risk assessment, knowledge of the relative toxicities of the congeners is required. These are expressed as "Toxicity Equivalence Factors" (TEFs). At present, TEFs are largely based on relative specific activities following intraperitoneal injection in a mouse bioassay rather than on acute toxicity determinations. A more relevant parameter for comparison would be median lethal doses via oral administration, since this is the route through which humans are exposed to PSTs. In the present study, the median lethal doses of gonyautoxin 5, gonyautoxin 6, decarbamoyl neosaxitoxin and of equilibrium mixtures of decarbamoyl gonyautoxins 2&3, C1&2 and C3&4 by oral administration to mice have been determined and compared with toxicities via intraperitoneal injection. The results indicate that the TEFs of several of these substances require revision in order to more accurately reflect the risk these toxins present to human health.
    Language English
    Publishing date 2017-02-21
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2518395-3
    ISSN 2072-6651 ; 2072-6651
    ISSN (online) 2072-6651
    ISSN 2072-6651
    DOI 10.3390/toxins9020073
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

  9. Article ; Online: Acute Toxicities of the Saxitoxin Congeners Gonyautoxin 5, Gonyautoxin 6, Decarbamoyl Gonyautoxin 2&3, Decarbamoyl Neosaxitoxin, C-1&2 and C-3&4 to Mice by Various Routes of Administration

    Andrew I. Selwood / Craig Waugh / David T. Harwood / Lesley L. Rhodes / John Reeve / Jim Sim / Rex Munday

    Toxins, Vol 9, Iss 2, p

    2017  Volume 73

    Abstract: Paralytic shellfish poisoning results from consumption of seafood naturally contaminated by saxitoxin and its congeners, the paralytic shellfish toxins (PSTs). The levels of such toxins are regulated internationally, and maximum permitted concentrations ... ...

    Abstract Paralytic shellfish poisoning results from consumption of seafood naturally contaminated by saxitoxin and its congeners, the paralytic shellfish toxins (PSTs). The levels of such toxins are regulated internationally, and maximum permitted concentrations in seafood have been established in many countries. A mouse bioassay is an approved method for estimating the levels of PSTs in seafood, but this is now being superseded in many countries by instrumental methods of analysis. Such analyses provide data on the levels of many PSTs in seafood, but for risk assessment, knowledge of the relative toxicities of the congeners is required. These are expressed as “Toxicity Equivalence Factors” (TEFs). At present, TEFs are largely based on relative specific activities following intraperitoneal injection in a mouse bioassay rather than on acute toxicity determinations. A more relevant parameter for comparison would be median lethal doses via oral administration, since this is the route through which humans are exposed to PSTs. In the present study, the median lethal doses of gonyautoxin 5, gonyautoxin 6, decarbamoyl neosaxitoxin and of equilibrium mixtures of decarbamoyl gonyautoxins 2&3, C1&2 and C3&4 by oral administration to mice have been determined and compared with toxicities via intraperitoneal injection. The results indicate that the TEFs of several of these substances require revision in order to more accurately reflect the risk these toxins present to human health.
    Keywords paralytic shellfish toxins ; gonyautoxins ; decarbamoyl neosaxitoxin ; decarbamoyl gonyautoxins ; C1& ; 2 ; C3& ; 4 ; acute toxicity ; toxicity equivalence factors ; oral exposure ; Medicine ; R
    Language English
    Publishing date 2017-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  10. Article ; Online: Identification of FleQ from Pseudomonas aeruginosa as a c-di-GMP-responsive transcription factor.

    Hickman, Jason W / Harwood, Caroline S

    Molecular microbiology

    2008  Volume 69, Issue 2, Page(s) 376–389

    Abstract: High levels of the intracellular signalling molecule cyclic diguanylate (c-di-GMP) supress motility ... part of the effect of c-di-GMP is on gene expression, but the mechanism involved is not known ... for any species. We have identified the protein FleQ as a c-di-GMP-responsive transcriptional regulator ...

    Abstract High levels of the intracellular signalling molecule cyclic diguanylate (c-di-GMP) supress motility and activate exopolysaccharide (EPS) production in a variety of bacterial species. In many bacteria part of the effect of c-di-GMP is on gene expression, but the mechanism involved is not known for any species. We have identified the protein FleQ as a c-di-GMP-responsive transcriptional regulator in Pseudomonas aeruginosa. FleQ is known to activate expression of flagella biosynthesis genes. Here we show that it also represses transcription of genes including the pel operon involved in EPS biosynthesis, and that this repression is relieved by c-di-GMP. Our in vivo data indicate that FleQ represses pel transcription and that pel transcription is not repressed when intracellular c-di-GMP levels are high. FleN, a known antiactivator of FleQ also participates in control of pel expression. In in vitro experiments we found that FleQ binds to pel promoter DNA and that this binding is inhibited by c-di-GMP. FleQ binds radiolabelled c-di-GMP in vitro. FleQ does not have amino acid motifs that resemble previously defined c-di-GMP binding domains. Our results show that FleQ is a new type of c-di-GMP binding protein that controls the transcriptional regulation of EPS biosynthesis genes in P. aeruginosa.
    MeSH term(s) Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Cyclic GMP/analogs & derivatives ; Cyclic GMP/metabolism ; DNA Transposable Elements ; DNA, Bacterial/metabolism ; Electrophoretic Mobility Shift Assay ; Gene Deletion ; Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; Models, Biological ; Mutagenesis, Insertional ; Promoter Regions, Genetic ; Protein Binding ; Pseudomonas aeruginosa/genetics ; Pseudomonas aeruginosa/growth & development ; Pseudomonas aeruginosa/physiology ; Trans-Activators/genetics ; Trans-Activators/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcription, Genetic
    Chemical Substances Bacterial Proteins ; DNA Transposable Elements ; DNA, Bacterial ; FleQ protein, Pseudomonas aeruginosa ; Trans-Activators ; Transcription Factors ; fleN protein, Pseudomonas aeruginosa ; bis(3',5')-cyclic diguanylic acid (61093-23-0) ; Cyclic GMP (H2D2X058MU)
    Language English
    Publishing date 2008-05-15
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 619315-8
    ISSN 1365-2958 ; 0950-382X
    ISSN (online) 1365-2958
    ISSN 0950-382X
    DOI 10.1111/j.1365-2958.2008.06281.x
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

To top