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  1. Article ; Online: iTRAQ-Based Quantitative Proteomic Analysis of Acinetobacter baumannii under Hypoxia and Normoxia Reveals the Role of OmpW as a Virulence Factor.

    Gil-Marqués, María Luisa / Pachón, Jerónimo / Smani, Younes

    Microbiology spectrum

    2022  Volume 10, Issue 2, Page(s) e0232821

    Abstract: Acinetobacter baumannii needs to adapt to hypoxia during infection. Understanding its proteome regulation during infection would allow us to determine new targets to develop novel treatments. iTRAQ proteomic analysis of A549 cell infection by the ATCC ... ...

    Abstract Acinetobacter baumannii needs to adapt to hypoxia during infection. Understanding its proteome regulation during infection would allow us to determine new targets to develop novel treatments. iTRAQ proteomic analysis of A549 cell infection by the ATCC 17978 strain was performed. A total of 175 proteins were differentially expressed under hypoxia versus normoxia. We selected the hypoxia-downregulated protein OmpW to analyze its role as a virulence factor. The loss of OmpW decreased the adherence and invasion of A. baumannii in these host cells, without affecting its bacterial growth. Moreover, A549 cell viability with ΔOmpW infection was higher than that with the wild-type strain. ΔOmpW presented less biofilm formation. Finally, the minimum lethal dose required by the ΔOmpW mutant was higher than that of the wild-type strain in a murine peritoneal sepsis model, with lower bacterial loads in tissues and fluids. Therefore, OmpW seems to be a virulence factor necessary for A. baumannii pathogenesis.
    MeSH term(s) Acinetobacter baumannii/genetics ; Acinetobacter baumannii/metabolism ; Animals ; Biofilms ; Hypoxia ; Mice ; Proteome/metabolism ; Proteomics ; Virulence Factors/genetics ; Virulence Factors/metabolism
    Chemical Substances Proteome ; Virulence Factors
    Language English
    Publishing date 2022-03-02
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2807133-5
    ISSN 2165-0497 ; 2165-0497
    ISSN (online) 2165-0497
    ISSN 2165-0497
    DOI 10.1128/spectrum.02328-21
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Antiviral activity of immunosuppressors alone and in combination against human adenovirus and cytomegalovirus.

    Carretero-Ledesma, Marta / Aguilar-Guisado, Manuela / Berastegui-Cabrera, Judith / Balsera-Manzanero, María / Pachón, Jerónimo / Cordero, Elisa / Sánchez-Céspedes, Javier

    International journal of antimicrobial agents

    2024  Volume 63, Issue 5, Page(s) 107116

    Abstract: Human adenovirus (HAdV) and cytomegalovirus (HCMV) cause high morbidity and mortality in patients undergoing solid organ transplantation (SOT) and haematopoietic stem cell transplantation (HSCT). Immunosuppressors are used universally to prevent graft-vs- ...

    Abstract Human adenovirus (HAdV) and cytomegalovirus (HCMV) cause high morbidity and mortality in patients undergoing solid organ transplantation (SOT) and haematopoietic stem cell transplantation (HSCT). Immunosuppressors are used universally to prevent graft-vs-host disease in HSCT and graft rejection in SOT. The long-term use of these drugs is associated with a high risk of infection, but there is also evidence of their specific interference with viral infection. This study evaluated the antiviral activity of immunosuppressors commonly used in clinical practice in SOT and HSCT recipients in vitro to determine whether their use could be associated with reduced risk of HAdV and HCMV infection. Cyclophosphamide, tacrolimus, cyclosporine, mycophenolic acid, methotrexate, everolimus and sirolimus presented antiviral activity, with 50% inhibitory concentration (IC
    MeSH term(s) Humans ; Immunosuppressive Agents/pharmacology ; Antiviral Agents/pharmacology ; Adenoviruses, Human/drug effects ; Cytomegalovirus/drug effects ; Drug Synergism ; Inhibitory Concentration 50 ; Mycophenolic Acid/pharmacology ; Tacrolimus/pharmacology ; Cyclosporine/pharmacology ; Cytomegalovirus Infections/drug therapy ; Cytomegalovirus Infections/virology ; Cytomegalovirus Infections/prevention & control
    Chemical Substances Immunosuppressive Agents ; Antiviral Agents ; Mycophenolic Acid (HU9DX48N0T) ; Tacrolimus (WM0HAQ4WNM) ; Cyclosporine (83HN0GTJ6D)
    Language English
    Publishing date 2024-02-23
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1093977-5
    ISSN 1872-7913 ; 0924-8579
    ISSN (online) 1872-7913
    ISSN 0924-8579
    DOI 10.1016/j.ijantimicag.2024.107116
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Concomitant administration of seasonal influenza and COVID-19 mRNA vaccines.

    Aydillo, Teresa / Balsera-Manzanero, Maria / Rojo-Fernandez, Amaya / Escalera, Alba / Salamanca-Rivera, Celia / Pachón, Jerónimo / Del Mar Muñoz-García, María / Sánchez-Cordero, María José / Sánchez-Céspedes, Javier / García-Sastre, Adolfo / Cordero, Elisa

    Emerging microbes & infections

    2024  Volume 13, Issue 1, Page(s) 2292068

    Abstract: Current clinical guidelines support the concomitant administration of seasonal influenza vaccines and COVID-19 mRNA boosters vaccine. Whether dual vaccination may impact vaccine immunogenicity due to an interference between influenza or SARS-CoV-2 ... ...

    Abstract Current clinical guidelines support the concomitant administration of seasonal influenza vaccines and COVID-19 mRNA boosters vaccine. Whether dual vaccination may impact vaccine immunogenicity due to an interference between influenza or SARS-CoV-2 antigens is unknown. We aimed to understand the impact of mRNA COVID-19 vaccines administered concomitantly on the immune response to influenza vaccines. For this, 128 volunteers were vaccinated during the 22-23 influenza season. Three groups of vaccination were assembled: FLU vaccine only (46, 35%)
    MeSH term(s) Humans ; Antibodies, Viral ; COVID-19/prevention & control ; COVID-19 Vaccines/administration & dosage ; Influenza A Virus, H3N2 Subtype ; Influenza Vaccines/administration & dosage ; Influenza, Human/prevention & control ; mRNA Vaccines ; Seasons ; Vaccination
    Chemical Substances Antibodies, Viral ; COVID-19 Vaccines ; Influenza Vaccines ; mRNA Vaccines
    Language English
    Publishing date 2024-01-18
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2681359-2
    ISSN 2222-1751 ; 2222-1751
    ISSN (online) 2222-1751
    ISSN 2222-1751
    DOI 10.1080/22221751.2023.2292068
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Inhibition of adenovirus transport from the endosome to the cell nucleus by rotenone.

    Balsera-Manzanero, María / Ghirga, Francesca / Ruiz-Molina, Ana / Mori, Mattia / Pachón, Jerónimo / Botta, Bruno / Cordero, Elisa / Quaglio, Deborah / Sánchez-Céspedes, Javier

    Frontiers in pharmacology

    2024  Volume 14, Page(s) 1293296

    Abstract: Regardless of the clinical impact of human adenovirus (HAdV) infections in the healthy population and its high morbidity in immunosuppressed patients, a specific treatment is still not yet available. In this study, we screened the CM1407 COST Action's ... ...

    Abstract Regardless of the clinical impact of human adenovirus (HAdV) infections in the healthy population and its high morbidity in immunosuppressed patients, a specific treatment is still not yet available. In this study, we screened the CM1407 COST Action's chemical library, comprising 1,233 natural products to identify compounds that restrict HAdV infection. Among them, we identified rotenolone, a compound that significantly inhibited HAdV infection. Next, we selected four isoflavonoid-type compounds (e.g., rotenone, deguelin, millettone, and tephrosin), namely rotenoids, structurally related to rotenolone in order to evaluate and characterized
    Language English
    Publishing date 2024-01-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2023.1293296
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Heteroleptic (S^C)-cyclometallated gold(III) complexes as novel antiviral agents.

    Balsera-Manzanero, María / Soengas, Raquel G / Carretero-Ledesma, Marta / Ratia, Carlos / Iglesias, M José / Pachón, Jerónimo / López-Ortiz, Fernando / Cordero, Elisa / Soto, Sara M / Sánchez-Céspedes, Javier

    Heliyon

    2024  Volume 10, Issue 6, Page(s) e27601

    Abstract: Despite the increasingly widespread clinical impact of adenovirus (HAdV) infections in healthy individuals and the associated high morbidity in immunosuppressed patients, particularly among the paediatric population, a specific treatment for this virus ... ...

    Abstract Despite the increasingly widespread clinical impact of adenovirus (HAdV) infections in healthy individuals and the associated high morbidity in immunosuppressed patients, particularly among the paediatric population, a specific treatment for this virus has yet to be developed. In this study, we report the anti-HAdV activity of sub-micromolar concentrations of four heteroleptic (C^S)-cycloaurated complexes bearing a single thiophosphinamide [
    Language English
    Publishing date 2024-03-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 2835763-2
    ISSN 2405-8440
    ISSN 2405-8440
    DOI 10.1016/j.heliyon.2024.e27601
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Efficacy of Lysophosphatidylcholine as Direct Treatment in Combination with Colistin against

    Miró-Canturri, Andrea / Ayerbe-Algaba, Rafael / Jiménez-Mejías, Manuel Enrique / Pachón, Jerónimo / Smani, Younes

    Antibiotics (Basel, Switzerland)

    2021  Volume 10, Issue 2

    Abstract: The stimulation of the immune response to prevent the progression of an infection may be an adjuvant to antimicrobial treatment. Here, we aimed to evaluate the efficacy of lysophosphatidylcholine (LPC) treatment in combination with colistin in murine ... ...

    Abstract The stimulation of the immune response to prevent the progression of an infection may be an adjuvant to antimicrobial treatment. Here, we aimed to evaluate the efficacy of lysophosphatidylcholine (LPC) treatment in combination with colistin in murine experimental models of severe infections by
    Language English
    Publishing date 2021-02-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2681345-2
    ISSN 2079-6382
    ISSN 2079-6382
    DOI 10.3390/antibiotics10020194
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Acidic Urine pH and Clinical Outcome of Lower Urinary Tract Infection in Kidney Transplant Recipients Treated with Ciprofloxacin and Fosfomycin.

    Herrera-Espejo, Soraya / Fontserè, Sara / Infante, Carmen / Suárez-Benjumea, Alejandro / Carretero-Ledesma, Marta / Suñer-Poblet, Marta / González-Corvillo, Carmen / Bernal, Gabriel / Martín-Gutiérrez, Guillermo / Pérez-Cáceres, Juan Antonio / Pachón, Jerónimo / Pachón-Ibáñez, María Eugenia / Cordero, Elisa

    Antibiotics (Basel, Switzerland)

    2024  Volume 13, Issue 2

    Abstract: Different factors, including antimicrobial resistance, may diminish the effectiveness of antibiotic therapy, challenging the management of post-transplant urinary tract infection (UTI). The association of acidic urine pH with microbiological and clinical ...

    Abstract Different factors, including antimicrobial resistance, may diminish the effectiveness of antibiotic therapy, challenging the management of post-transplant urinary tract infection (UTI). The association of acidic urine pH with microbiological and clinical outcomes was evaluated after fosfomycin or ciprofloxacin therapy in 184 kidney transplant recipients (KTRs) with UTI episodes by
    Language English
    Publishing date 2024-01-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2681345-2
    ISSN 2079-6382
    ISSN 2079-6382
    DOI 10.3390/antibiotics13020116
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: A lipopolysaccharide-free outer membrane vesicle vaccine protects against Acinetobacter baumannii infection

    Pulido, Marina R / García-Quintanilla, Meritxell / Pachón, Jerónimo / McConnell, Michael J

    Vaccine. 2020 Jan. 22, v. 38, no. 4

    2020  

    Abstract: Outer membrane vesicles (OMVs) were isolated from an Acinetobacter strain deficient in lipopolysaccharide (LPS) due to a mutation in lpxD (IB010). Two immunizations with 10 μg of IB010 OMVs elicited total IgG, IgM, IgG1 and IgG2c titers similar to those ... ...

    Abstract Outer membrane vesicles (OMVs) were isolated from an Acinetobacter strain deficient in lipopolysaccharide (LPS) due to a mutation in lpxD (IB010). Two immunizations with 10 μg of IB010 OMVs elicited total IgG, IgM, IgG1 and IgG2c titers similar to those observed after immunization with OMVs derived from the parental strain (ATCC 19606), and IB010 OMVs plus purified LPS. Immunization with IB010 OMVs resulted in significantly reduced post-infection spleen bacterial loads and serum IL-1β and IL-6 levels compared to control mice in a disseminated sepsis model. Mice immunized with 10 μg IB010 OMVs demonstrated significant, but partial, protection (75%) against infection, whereas mice immunized with ATCC 19606 OMVs or IB010 OMVs plus purified LPS were completely protected. Immunization of mice with 100 μg of IB010 OMVs completely protected mice from infection. This study demonstrates that LPS deficient A. baumannii produces OMVs, and that immunization with these OMVs elicits protective immunity against infection.
    Keywords Acinetobacter baumannii ; blood serum ; immunity ; immunization ; immunoglobulin G ; immunoglobulin M ; interleukin-1beta ; interleukin-6 ; lipopolysaccharides ; microbial load ; models ; mutation ; sepsis (infection) ; spleen ; vaccines
    Language English
    Dates of publication 2020-0122
    Size p. 719-724.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2019.11.043
    Database NAL-Catalogue (AGRICOLA)

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  9. Article ; Online: Repositioning rafoxanide to treat Gram-negative bacilli infections.

    Miró-Canturri, Andrea / Ayerbe-Algaba, Rafael / Villodres, Ángel Rodríguez / Pachón, Jerónimo / Smani, Younes

    The Journal of antimicrobial chemotherapy

    2020  Volume 75, Issue 7, Page(s) 1895–1905

    Abstract: Objectives: Repurposing drugs provides a new approach to the fight against MDR Gram-negative bacilli (MDR-GNB). Rafoxanide, a veterinary antihelminthic drug, has shown antibacterial activity in vitro against Gram-positive bacteria. We aimed to analyse ... ...

    Abstract Objectives: Repurposing drugs provides a new approach to the fight against MDR Gram-negative bacilli (MDR-GNB). Rafoxanide, a veterinary antihelminthic drug, has shown antibacterial activity in vitro against Gram-positive bacteria. We aimed to analyse the in vitro and in vivo efficacy of rafoxanide in combination with colistin against colistin-susceptible (Col-S) and colistin-resistant (Col-R) GNB.
    Methods: A collection of Col-S and Col-R Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae were used. Chequerboard and time-kill curve analyses were performed to determine the synergy between rafoxanide and colistin. Changes in membrane structure and permeability were analysed using transmission electron microscopy and fluorescence assays. A murine peritoneal sepsis model using Col-R strains of these pathogens was performed to study the efficacy of rafoxanide (10 mg/kg/24 h, IV), colistimethate sodium (CMS) (20 mg/kg/8 h, intraperitoneally) and rafoxanide (10 mg/kg/24 h, IV) plus CMS (20 mg/kg/8 h, intraperitoneally) for 72 h.
    Results: Rafoxanide showed MICs ≥256 mg/L for all Col-S and Col-R strains. Chequerboard and time-kill curve analyses showed that rafoxanide (1 mg/L) is more synergistic with colistin against Col-R than Col-S strains. Col-R, but not Col-S, strains treated with rafoxanide demonstrated higher membrane permeabilization. Transmission electron microscopy visualization confirmed that Col-R strains suffer morphological changes. In the murine peritoneal sepsis model with Col-R strains, rafoxanide plus CMS, compared with CMS alone, increased mouse survival to 53.8% and 73.3%, and reduced bacterial loads in tissues and blood between 2.34 and 4.99 log10 cfu/g or mL, respectively.
    Conclusions: Rafoxanide repurposing, as monotherapy and in combination with CMS, may address the urgent need for new treatments for infections caused by MDR-GNB.
    MeSH term(s) Acinetobacter baumannii ; Animals ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Colistin/pharmacology ; Drug Resistance, Multiple, Bacterial ; Drug Synergism ; Gram-Negative Bacteria ; Mice ; Microbial Sensitivity Tests ; Rafoxanide/pharmacology
    Chemical Substances Anti-Bacterial Agents ; Rafoxanide (22F4FLA7DH) ; Colistin (Z67X93HJG1)
    Language English
    Publishing date 2020-04-02
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 191709-2
    ISSN 1460-2091 ; 0305-7453
    ISSN (online) 1460-2091
    ISSN 0305-7453
    DOI 10.1093/jac/dkaa103
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Structure-Activity Relationship Studies on Diversified Salicylamide Derivatives as Potent Inhibitors of Human Adenovirus Infection.

    Xu, Jimin / Berastegui-Cabrera, Judith / Chen, Haiying / Pachón, Jerónimo / Zhou, Jia / Sánchez-Céspedes, Javier

    Journal of medicinal chemistry

    2020  Volume 63, Issue 6, Page(s) 3142–3160

    Abstract: The effective treatment of adenovirus (HAdV) infections in immunocompromised patients still poses great challenges. Herein, we reported our continued efforts to optimize a series of salicylamide derivatives as potent inhibitors of HAdV infection. Of ... ...

    Abstract The effective treatment of adenovirus (HAdV) infections in immunocompromised patients still poses great challenges. Herein, we reported our continued efforts to optimize a series of salicylamide derivatives as potent inhibitors of HAdV infection. Of these, nine compounds (
    MeSH term(s) A549 Cells ; Adenoviruses, Human/drug effects ; Antiviral Agents/chemical synthesis ; Antiviral Agents/pharmacology ; Antiviral Agents/toxicity ; DNA/metabolism ; DNA Replication/drug effects ; Humans ; Microbial Sensitivity Tests ; Molecular Structure ; Salicylamides/chemical synthesis ; Salicylamides/pharmacology ; Salicylamides/toxicity ; Structure-Activity Relationship ; Virus Internalization/drug effects
    Chemical Substances Antiviral Agents ; Salicylamides ; DNA (9007-49-2)
    Language English
    Publishing date 2020-02-28
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.9b01950
    Database MEDical Literature Analysis and Retrieval System OnLINE

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