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  1. AU="Fernandez-Soto, Paulina"
  2. AU="Asplund, Kjell"
  3. AU="Yamaguchi, Tatsuya"
  4. AU="Kho, T K"
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  1. Article ; Online: Cinnamomum

    Fernandez-Soto, Paulina / Celi, Diana / Tejera, Eduardo / Alvarez-Suarez, José Miguel / Machado, António

    Molecules (Basel, Switzerland)

    2023  Volume 28, Issue 2

    Abstract: Horchata, a herbal infusion drink from Ecuador containing a mixture of medicinal plants, has been reported to exhibit anti-inflammatory, analgesic, diuretic, and antioxidant activity. The antibacterial activity of each of the plants contained in the ... ...

    Abstract Horchata, a herbal infusion drink from Ecuador containing a mixture of medicinal plants, has been reported to exhibit anti-inflammatory, analgesic, diuretic, and antioxidant activity. The antibacterial activity of each of the plants contained in the horchata mixture has not been fully evaluated. Thus, in this study, we analysed the antibacterial activity of 21 plants used in horchata, collected from the Ecuadorian Andes region, against bacterial strains of clinical importance. The methanolic extract of
    MeSH term(s) Staphylococcus aureus ; Pelargonium ; Cinnamomum/chemistry ; Methicillin-Resistant Staphylococcus aureus ; Plant Extracts/pharmacology ; Plant Extracts/chemistry ; Tandem Mass Spectrometry ; Gas Chromatography-Mass Spectrometry ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/chemistry ; Microbial Sensitivity Tests ; Tannins
    Chemical Substances Plant Extracts ; Anti-Bacterial Agents ; Tannins
    Language English
    Publishing date 2023-01-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules28020693
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.MO 81: Show issues

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  2. Article ; Online: Expression and purification of soluble recombinant SapM from Mycobacterium tuberculosis.

    Fernandez-Soto, Paulina / Cavet, Jennifer S / Tabernero, Lydia

    Protein expression and purification

    2020  Volume 174, Page(s) 105663

    Abstract: SapM from Mycobacterium tuberculosis is a secreted phosphatase critical for pathogen survival inside the host, representing an attractive target for the development of anti-tuberculosis drugs. The main limitation to biochemical and structural studies of ... ...

    Abstract SapM from Mycobacterium tuberculosis is a secreted phosphatase critical for pathogen survival inside the host, representing an attractive target for the development of anti-tuberculosis drugs. The main limitation to biochemical and structural studies of SapM has been the lack of a suitable protocol to produce soluble recombinant protein. The aim of the present work was to produce SapM in Escherichia coli in a soluble and catalytically active form. We describe here the construct design, expression and purification of soluble SapM using Sarkosyl as a solubility-enhancing agent and auto-induction media. We demonstrate that solubilisation of the recombinant protein with Sarkosyl, and further purification, yields a catalytically active enzyme with high purity and monodisperse. The identity and molecular weight of the recombinant SapM was confirmed by mass spectrometry analyses, and we provide evidence that SapM behaves as a monomer in solution. Overall, this work lays the foundation for further studies to exploit SapM as a drug target, and provides a protocol for producing active and soluble recombinant enzymes that are hard to solubilise in E. coli.
    MeSH term(s) Bacterial Proteins/biosynthesis ; Bacterial Proteins/chemistry ; Bacterial Proteins/genetics ; Bacterial Proteins/isolation & purification ; Escherichia coli/enzymology ; Escherichia coli/genetics ; Gene Expression ; Mycobacterium tuberculosis/enzymology ; Mycobacterium tuberculosis/genetics ; Phosphoric Monoester Hydrolases/biosynthesis ; Phosphoric Monoester Hydrolases/chemistry ; Phosphoric Monoester Hydrolases/genetics ; Phosphoric Monoester Hydrolases/isolation & purification ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/chemistry ; Recombinant Proteins/genetics ; Recombinant Proteins/isolation & purification ; Solubility
    Chemical Substances Bacterial Proteins ; Recombinant Proteins ; Phosphoric Monoester Hydrolases (EC 3.1.3.2)
    Language English
    Publishing date 2020-05-06
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1055455-5
    ISSN 1096-0279 ; 1046-5928
    ISSN (online) 1096-0279
    ISSN 1046-5928
    DOI 10.1016/j.pep.2020.105663
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3084: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: Mechanism of catalysis and inhibition of Mycobacterium tuberculosis SapM, implications for the development of novel antivirulence drugs.

    Fernandez-Soto, Paulina / Bruce, Alexander J E / Fielding, Alistair J / Cavet, Jennifer S / Tabernero, Lydia

    Scientific reports

    2019  Volume 9, Issue 1, Page(s) 10315

    Abstract: Mycobacterium tuberculosis (Mtb) SapM is a secreted virulence factor critical for intracellular survival of the pathogen. The role of SapM in phagosome maturation arrest in host macrophages suggests its potential as a drug target to assist in the ... ...

    Abstract Mycobacterium tuberculosis (Mtb) SapM is a secreted virulence factor critical for intracellular survival of the pathogen. The role of SapM in phagosome maturation arrest in host macrophages suggests its potential as a drug target to assist in the clearance of tuberculosis infection. However, the mechanism of action of SapM at the molecular level remains unknown. In this study, we provide new insights into the mechanism of catalysis, substrate specificity and inhibition of SapM, and we identify the critical residues for catalysis and substrate binding. Our findings demonstrate that SapM is an atypical monoester alkaline phosphatase, with a serine-based mechanism of catalysis probably metal-dependent. Particularly relevant to SapM function and pathogenesis, is its activity towards PI(4,5)P
    MeSH term(s) Acid Phosphatase/antagonists & inhibitors ; Acid Phosphatase/chemistry ; Acid Phosphatase/genetics ; Antitubercular Agents/pharmacology ; Ascorbic Acid/analogs & derivatives ; Ascorbic Acid/pharmacology ; Bacterial Proteins/antagonists & inhibitors ; Bacterial Proteins/chemistry ; Bacterial Proteins/genetics ; Catalysis ; Catalytic Domain ; Humans ; Inhibitory Concentration 50 ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/pathogenicity ; Phosphatidylinositols/metabolism ; Substrate Specificity ; THP-1 Cells ; Virulence/drug effects
    Chemical Substances Antitubercular Agents ; Bacterial Proteins ; Phosphatidylinositols ; ascorbate-2-phosphate (23313-12-4) ; Acid Phosphatase (EC 3.1.3.2) ; Ascorbic Acid (PQ6CK8PD0R)
    Language English
    Publishing date 2019-07-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-019-46731-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Influence of Altitudes and Development Stages on the Chemical Composition, Antioxidant, and Antimicrobial Capacity of the Wild Andean Blueberry (

    Guevara-Terán, Mabel / Padilla-Arias, Katherine / Beltrán-Novoa, Andrea / González-Paramás, Ana M / Giampieri, Francesca / Battino, Maurizio / Vásquez-Castillo, Wilson / Fernandez-Soto, Paulina / Tejera, Eduardo / Alvarez-Suarez, José M

    Molecules (Basel, Switzerland)

    2022  Volume 27, Issue 21

    Abstract: The chemical composition and biological capacities of berries depend on environmental parameters, maturity, and location. The Andean blueberry ( ...

    Abstract The chemical composition and biological capacities of berries depend on environmental parameters, maturity, and location. The Andean blueberry (
    MeSH term(s) Blueberry Plants/chemistry ; Vaccinium/chemistry ; Antioxidants/chemistry ; Anthocyanins/chemistry ; Altitude ; Anti-Bacterial Agents/analysis ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Fruit/chemistry ; Anti-Infective Agents/pharmacology ; Anti-Infective Agents/analysis
    Chemical Substances Antioxidants ; Anthocyanins ; Anti-Bacterial Agents ; Anti-Infective Agents
    Language English
    Publishing date 2022-11-03
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules27217525
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.MO 81: Show issues

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  5. Article ; Online: Discovery of uncompetitive inhibitors of SapM that compromise intracellular survival of Mycobacterium tuberculosis.

    Fernández-Soto, Paulina / Casulli, Joshua / Solano-Castro, Danilo / Rodríguez-Fernández, Pablo / Jowitt, Thomas A / Travis, Mark A / Cavet, Jennifer S / Tabernero, Lydia

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 7667

    Abstract: SapM is a secreted virulence factor from Mycobacterium tuberculosis critical for pathogen survival and persistence inside the host. Its full potential as a target for tuberculosis treatment has not yet been exploited because of the lack of potent ... ...

    Abstract SapM is a secreted virulence factor from Mycobacterium tuberculosis critical for pathogen survival and persistence inside the host. Its full potential as a target for tuberculosis treatment has not yet been exploited because of the lack of potent inhibitors available. By screening over 1500 small molecules, we have identified new potent and selective inhibitors of SapM with an uncompetitive mechanism of inhibition. The best inhibitors share a trihydroxy-benzene moiety essential for activity. Importantly, the inhibitors significantly reduce mycobacterial burden in infected human macrophages at 1 µM, and they are selective with respect to other mycobacterial and human phosphatases. The best inhibitor also reduces intracellular burden of Francisella tularensis, which secretes the virulence factor AcpA, a homologue of SapM, with the same mechanism of catalysis and inhibition. Our findings demonstrate that inhibition of SapM with small molecule inhibitors is efficient in reducing intracellular mycobacterial survival in host macrophages and confirm SapM as a potential therapeutic target. These initial compounds have favourable physico-chemical properties and provide a basis for exploration towards the development of new tuberculosis treatments. The efficacy of a SapM inhibitor in reducing Francisella tularensis intracellular burden suggests the potential for developing broad-spectrum antivirulence agents to treat microbial infections.
    MeSH term(s) Alkaline Phosphatase/antagonists & inhibitors ; Francisella tularensis/enzymology ; Humans ; Molecular Targeted Therapy ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/pathogenicity ; Small Molecule Libraries ; Structure-Activity Relationship ; Tuberculosis/drug therapy ; Virulence Factors/antagonists & inhibitors
    Chemical Substances Small Molecule Libraries ; Virulence Factors ; Alkaline Phosphatase (EC 3.1.3.1)
    Language English
    Publishing date 2021-04-07
    Publishing country England
    Document type Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-87117-x
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Infant Alveolar Macrophages Are Unable to Effectively Contain

    Goenka, Anu / Prise, Ian E / Connolly, Emma / Fernandez-Soto, Paulina / Morgan, David / Cavet, Jennifer S / Grainger, John R / Nichani, Jaya / Arkwright, Peter D / Hussell, Tracy

    Frontiers in immunology

    2020  Volume 11, Page(s) 486

    Abstract: Infants are more likely to develop lethal disseminated forms of tuberculosis compared with older children and adults. The reasons for this are currently unknown. In this study we test the hypothesis that antimycobacterial function is impaired in infant ... ...

    Abstract Infants are more likely to develop lethal disseminated forms of tuberculosis compared with older children and adults. The reasons for this are currently unknown. In this study we test the hypothesis that antimycobacterial function is impaired in infant alveolar macrophages (AMϕs) compared with those of adults. We develop a method of obtaining AMϕs from healthy infants using rigid bronchoscopy and incubate the AMϕs with live virulent
    MeSH term(s) Adult ; Aged ; Bronchoalveolar Lavage Fluid ; Chemokines/biosynthesis ; Chemokines/genetics ; Chemotaxis/genetics ; Disease Susceptibility ; Gene Expression Regulation ; Gene Ontology ; Humans ; Immune System/growth & development ; Infant ; Macrophage Activation ; Macrophages, Alveolar/physiology ; Middle Aged ; Mycobacterium tuberculosis/physiology ; Phagocytosis ; RNA, Messenger/biosynthesis ; RNA-Seq
    Chemical Substances Chemokines ; RNA, Messenger
    Language English
    Publishing date 2020-03-24
    Publishing country Switzerland
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.00486
    Database MEDical Literature Analysis and Retrieval System OnLINE

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