scholarly journals Systematic Analysis of the SsrAB Virulon of Salmonella enterica

2009 ◽  
Vol 78 (1) ◽  
pp. 49-58 ◽  
Author(s):  
Xin Xu ◽  
Michael Hensel
Keyword(s):  
Salmonella Enterica ◽  
Rational Design ◽  
Regulatory System ◽  
Effector Proteins ◽  
High Expression ◽  
Systematic Analysis ◽  
Expression Levels ◽  
Cell Functions

ABSTRACT Intracellular Salmonella enterica serovar Typhimurium deploys the Salmonella pathogenicity island 2 (SPI2)-encoded type III secretion system (T3SS) to modify host cell functions and accomplish intracellular replication. This virulence function is controlled by the two-component system SsrAB that regulates the expression of several operons in SPI2 and, in addition, a large number of genes for non-SPI2-encoded effector proteins. Here, we analyzed the relative expression levels of members of the SsrAB virulon. We used a novel reporter fusion strategy for single-copy chromosomal fusions, all done in an identical manner in order to enable direct quantitative comparison. We observed very high expression levels for sseJ and sifA; high expression levels for ssaG, steC, sseL, and sopD2; moderate expression levels for ssaB, sseA, sseG, sifB, pipB2, and sspH1; and low expression levels for sspH2, sseI, slrP, sseK1, sseK2, pipB, and gogB. The expression of the SsrAB virulon was highly dependent on the function of SsrB but also required EnvR/OmpZ. Deletion of PhoP, part of the global regulatory system PhoPQ, resulted in highly delayed expression of the SsrAB virulon under in vitro conditions; however, maximal expression was similar to that in a wild-type background. The expression levels of SsrAB-dependent genes in intracellular bacteria were in good agreement with in vitro analyses. We provide here a comprehensive and fully comparable analysis of the expression of genes in the SsrAB virulon. This information will be of interest for the selection of in vivo-activated promoters, for example, for rational design of recombinant vaccines.

scholarly journals Implication of Quorum Sensing in Salmonella enterica Serovar Typhimurium Virulence: the luxS Gene Is Necessary for Expression of Genes in Pathogenicity Island 1

2007 ◽  
Vol 75 (10) ◽  
pp. 4885-4890 ◽  
Author(s):  
Jeongjoon Choi ◽  
Dongwoo Shin ◽  
Sangryeol Ryu
Keyword(s):  
Quorum Sensing ◽  
Salmonella Enterica ◽  
Biological Significance ◽  
Regulatory System ◽  
Pathogenicity Island ◽  
Plasmid Copy ◽  
Signal Molecule ◽  
Synthetic Signal

ABSTRACT Despite the fact that the regulatory system sensing density of cell population and its signaling molecule have been identified in Salmonella enterica, the biological significance of this phenomenon termed as quorum sensing remains unknown. In this report, we provide evidence that the luxS gene is necessary for Salmonella virulence phenotypes. Transcription assays showed that the cell-density-dependent induction of the invF gene was abolished in a Salmonella strain with the luxS gene deleted. The effect of the luxS deletion was also investigated in other InvF-regulated genes expressed from Salmonella pathogenicity island 1 (SPI-1). The decreased expression of SPI-1 genes in the strain with luxS deleted could be restored by either the addition of a synthetic signal molecule or the introduction of a plasmid copy of the luxS gene. Thus, the reduced expression of invF and its regulated genes in Salmonella cells lacking quorum sensing resulted in the attenuation of virulence phenotypes both in vitro and in vivo.

scholarly journals Antioxidant Potential of Psychotropic Drugs: From Clinical Evidence to In Vitro and In Vivo Assessment and toward a New Challenge for in Silico Molecular Design

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 714 ◽  
Author(s):  
Giovanni Ribaudo ◽  
Marco Bortoli ◽  
Chiara Pavan ◽  
Giuseppe Zagotto ◽  
Laura Orian
Keyword(s):  
Oxidative Stress ◽  
In Silico ◽  
Rational Design ◽  
Molecular Design ◽  
Antioxidant Potential ◽  
Oxidative Stress Biomarkers ◽  
Systematic Analysis ◽  
Antioxidant Supplements

Due to high oxygen consumption, the brain is particularly vulnerable to oxidative stress, which is considered an important element in the etiopathogenesis of several mental disorders, including schizophrenia, depression and dependencies. Despite the fact that it is not established yet whether oxidative stress is a cause or a consequence of clinic manifestations, the intake of antioxidant supplements in combination with the psychotropic therapy constitutes a valuable solution in patients’ treatment. Anyway, some drugs possess antioxidant capacity themselves and this aspect is discussed in this review, focusing on antipsychotics and antidepressants. In the context of a collection of clinical observations, in vitro and in vivo results are critically reported, often highlighting controversial aspects. Finally, a new challenge is discussed, i.e., the possibility of assessing in silico the antioxidant potential of these drugs, exploiting computational chemistry methodologies and machine learning. Despite the physiological environment being incredibly complex and the detection of meaningful oxidative stress biomarkers being all but an easy task, a rigorous and systematic analysis of the structural and reactivity properties of antioxidant drugs seems to be a promising route to better interpret therapeutic outcomes and provide elements for the rational design of novel drugs.

scholarly journals Identification of cptA, a PmrA-Regulated Locus Required for Phosphoethanolamine Modification of the Salmonella enterica Serovar Typhimurium Lipopolysaccharide Core

2005 ◽  
Vol 187 (10) ◽  
pp. 3391-3399 ◽  
Author(s):  
R. Tamayo ◽  
B. Choudhury ◽  
A. Septer ◽  
M. Merighi ◽  
R. Carlson ◽  
...  
Keyword(s):  
Surface Charge ◽  
Salmonella Enterica ◽  
Lipid A ◽  
Salmonella Enterica Serovar Typhimurium ◽  
Regulatory System ◽  
Polymyxin B ◽  
Serovar Typhimurium ◽  
Antimicrobial Peptide Resistance

ABSTRACT In response to the in vivo environment, the Salmonella enterica serovar Typhimurium lipopolysaccharide (LPS) is modified. These modifications are controlled in part by the two-component regulatory system PmrA-PmrB, with the addition of 4-aminoarabinose (Ara4N) to the lipid A and phosphoethanolamine (pEtN) to the lipid A and core. Here we demonstrate that the PmrA-regulated STM4118 (cptA) gene is necessary for the addition of pEtN to the LPS core. pmrC, a PmrA-regulated gene necessary for the addition of pEtN to lipid A, did not affect core pEtN addition. Although imparting a similar surface charge modification as Ara4N, which greatly affects polymyxin B resistance and murine virulence, neither pmrC nor cptA plays a dramatic role in antimicrobial peptide resistance in vitro or virulence in the mouse model. Therefore, factors other than surface charge/electrostatic interaction contribute to resistance to antimicrobial peptides such as polymyxin B.

scholarly journals Mutational Analysis of the Residue at Position 48 in the Salmonella enterica Serovar Typhimurium PhoQ Sensor Kinase

2003 ◽  
Vol 185 (6) ◽  
pp. 1935-1941 ◽  
Author(s):  
Sarah Sanowar ◽  
Alexandre Martel ◽  
Hervé Le Moual
Keyword(s):  
Amino Acid ◽  
Phosphatase Activity ◽  
Salmonella Enterica ◽  
Mutational Analysis ◽  
Regulatory System ◽  
Single Amino Acid ◽  
Serovar Typhimurium ◽  
Constitutively Active

ABSTRACT The PhoP/PhoQ two-component regulatory system of Salmonella enterica serovar Typhimurium plays an essential role in controlling virulence by mediating the adaptation to Mg2+ depletion. The pho-24 allele of phoQ harbors a single amino acid substitution (T48I) in the periplasmic domain of the PhoQ histidine kinase sensor. This mutation has been shown to increase net phosphorylation of the PhoP response regulator. We analyzed the effect on signaling by PhoP/PhoQ of various amino acid substitutions at this position (PhoQ-T48X [X = A, S, V, I, or L]). Mutations T48V, T48I, and T48L were found to affect signaling by PhoP/PhoQ both in vivo and in vitro. Mutations PhoQ-T48V and PhoQ-T48I increased both the expression of the mgtA::lacZ transcriptional fusion and the net phosphorylation of PhoP, conferring to cells a PhoP constitutively active phenotype. In contrast, mutation PhoQ-T48L barely responded to changes in the concentration of external Mg2+, in vivo and in vitro, conferring to cells a PhoP constitutively inactive phenotype. By analyzing in vitro the individual catalytic activities of the PhoQ-T48X sensors, we found that the PhoP constitutively active phenotype observed for the PhoQ-T48V and PhoQ-T48I proteins is solely due to decreased phosphatase activity. In contrast, the PhoP constitutively inactive phenotype observed for the PhoQ-T48L mutant resulted from both decreased autokinase activity and increased phosphatase activity. Our data are consistent with a model in which the residue at position 48 of PhoQ contributes to a conformational switch between kinase- and phosphatase-dominant states.

Defibrotide Inhibits Platelet Activation by Cathepsin G Released From Stimulated Polymorphonuclear Leukocytes

1992 ◽  
Vol 67 (06) ◽  
pp. 660-664 ◽  
Author(s):  
Virgilio Evangelista ◽  
Paola Piccardoni ◽  
Giovanni de Gaetano ◽  
Chiara Cerletti
Keyword(s):  
Platelet Activation ◽  
Polymorphonuclear Leukocytes ◽  
Direct Interaction ◽  
Cathepsin G ◽  
In Vivo Test ◽  
Cell Functions ◽  
Test Models ◽  
Antithrombotic Effects

SummaryDefibrotide is a polydeoxyribonucleotide with antithrombotic effects in experimental animal models. Most of the actions of this drug have been observed in in vivo test models but no effects have been reported in in vitro systems. In this paper we demonstrate that defibrotide interferes with polymorphonuclear leukocyte-induced human platelet activation in vitro. This effect was not related to any direct interaction with polymorphonuclear leukocytes or platelets, but was due to the inhibition of cathepsin G, the main biochemical mediator of this cell-cell cooperation. Since cathepsin G not only induces platelet activation but also affects some endothelial cell functions, the anticathepsin G activity of defibrotide could help to explain the antithrombotic effect of this drug.

THYROID STIMULATORS AND THYROID STIMULATION

1971 ◽  
Vol 66 (3) ◽  
pp. 558-576 ◽  
Author(s):  
Gerald Burke
Keyword(s):  
Regulatory System ◽  
Control Site ◽  
Thyroid Cell ◽  
Primary Control ◽  
Physico Chemical ◽  
Site Of Action ◽  
Long Acting

ABSTRACT A long-acting thyroid stimulator (LATS), distinct from pituitary thyrotrophin (TSH), is found in the serum of some patients with Graves' disease. Despite the marked physico-chemical and immunologic differences between the two stimulators, both in vivo and in vitro studies indicate that LATS and TSH act on the same thyroidal site(s) and that such stimulation does not require penetration of the thyroid cell. Although resorption of colloid and secretion of thyroid hormone are early responses to both TSH and LATS, available evidence reveals no basic metabolic pathway which must be activated by these hormones in order for iodination reactions to occur. Cyclic 3′, 5′-AMP appears to mediate TSH and LATS effects on iodination reactions but the role of this compound in activating thyroidal intermediary metabolism is less clear. Based on the evidence reviewed herein, it is suggested that the primary site of action of thyroid stimulators is at the cell membrane and that beyond the(se) primary control site(s), there exists a multifaceted regulatory system for thyroid hormonogenesis and cell growth.

Metabolomics of Healthy Berry Fruits

2019 ◽  
Vol 25 (37) ◽  
pp. 4888-4902 ◽  
Author(s):  
Gilda D'Urso ◽  
Sonia Piacente ◽  
Cosimo Pizza ◽  
Paola Montoro
Keyword(s):  
Biological Activities ◽  
Biologically Active ◽  
In Vivo Studies ◽  
Bioactive Metabolites ◽  
Active Metabolites ◽  
Positive Effects ◽  
Cell Functions ◽  
Berry Fruits

The consumption of berry-type fruits has become very popular in recent years because of their positive effects on human health. Berries are in fact widely known for their health-promoting benefits, including prevention of chronic disease, cardiovascular disease and cancer. Berries are a rich source of bioactive metabolites, such as vitamins, minerals, and phenolic compounds, mainly anthocyanins. Numerous in vitro and in vivo studies recognized the health effects of berries and their function as bioactive modulators of various cell functions associated with oxidative stress. Plants have one of the largest metabolome databases, with over 1200 papers on plant metabolomics published only in the last decade. Mass spectrometry (MS) and NMR (Nuclear Magnetic Resonance) are the most important analytical technologies on which the emerging ''omics'' approaches are based. They may provide detection and quantization of thousands of biologically active metabolites from a tissue, working in a ''global'' or ''targeted'' manner, down to ultra-trace levels. In the present review, we highlighted the use of MS and NMR-based strategies and Multivariate Data Analysis for the valorization of berries known for their biological activities, important as food and often used in the preparation of nutraceutical formulations.

scholarly journals 99mTc Labelling Strategies for the Development of Potential Nitroimidazolic Hypoxia Imaging Agents

Inorganics ◽  
2019 ◽  
Vol 7 (11) ◽  
pp. 128 ◽  
Author(s):  
Giglio ◽  
Rey
Keyword(s):  
Rational Design ◽  
Biological Properties ◽  
Fine Tuning ◽  
Oxidation States ◽  
Hypoxia Imaging ◽  
Biological Target ◽  
99Mtc Radiopharmaceuticals ◽  
99Mtc Labelling

Technetium-99m has a rich coordination chemistry that offers many possibilities in terms of oxidation states and donor atom sets. Modifications in the structure of the technetium complexes could be very useful for fine tuning the physicochemical and biological properties of potential 99mTc radiopharmaceuticals. However, systematic study of the influence of the labelling strategy on the “in vitro” and “in vivo” behaviour is necessary for a rational design of radiopharmaceuticals. Herein we present a review of the influence of the Tc complexes’ molecular structure on the biodistribution and the interaction with the biological target of potential nitroimidazolic hypoxia imaging radiopharmaceuticals presented in the literature from 2010 to the present. Comparison with the gold standard [18F]Fluoromisonidazole (FMISO) is also presented.

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