Articles producció científica> Ciències Mèdiques Bàsiques

RNAi-Based Functional Genomics Identifies New Virulence Determinants in Mucormycosis

  • Identification data

    Identifier: imarina:5130748
    Authors:
    Trieu TA, Navarro-Mendoza MI, Pérez-Arques C, Sanchis M, Capilla J, Navarro-Rodriguez P, Lopez-Fernandez L, Torres-Martínez S, Garre V, Ruiz-Vázquez RM, Nicolás FE
    Abstract:
    Mucorales are an emerging group of human pathogens that are responsible for the lethal disease mucormycosis. Unfortunately, functional studies on the genetic factors behind the virulence of these organisms are hampered by their limited genetic tractability, since they are reluctant to classical genetic tools like transposable elements or gene mapping. Here, we describe an RNAi-based functional genomic platform that allows the identification of new virulence factors through a forward genetic approach firstly described in Mucorales. This platform contains a whole-genome collection of Mucor circinelloides silenced transformants that presented a broad assortment of phenotypes related to the main physiological processes in fungi, including virulence, hyphae morphology, mycelial and yeast growth, carotenogenesis and asexual sporulation. Selection of transformants with reduced virulence allowed the identification of mcplD, which encodes a Phospholipase D, and mcmyo5, encoding a probably essential cargo transporter of the Myosin V family, as required for a fully virulent phenotype of M. circinelloides. Knock-out mutants for those genes showed reduced virulence in both Galleria mellonella and Mus musculus models, probably due to a delayed germination and polarized growth within macrophages. This study provides a robust approach to study virulence in Mucorales and as a proof of concept identified new virulence determinants in M. circinelloides that could represent promising targets for future antifungal therapies.
  • Others:

    Author, as appears in the article.: Trieu TA, Navarro-Mendoza MI, Pérez-Arques C, Sanchis M, Capilla J, Navarro-Rodriguez P, Lopez-Fernandez L, Torres-Martínez S, Garre V, Ruiz-Vázquez RM, Nicolás FE
    Department: Ciències Mèdiques Bàsiques
    URV's Author/s: Alkhoury, Nadine / Capilla Luque, Javier / Sanchis Talón, Marta
    Keywords: Responses Phospholipase-d Oryzae Gene Fungus Expression Components Clinical-manifestations Cells
    Abstract: Mucorales are an emerging group of human pathogens that are responsible for the lethal disease mucormycosis. Unfortunately, functional studies on the genetic factors behind the virulence of these organisms are hampered by their limited genetic tractability, since they are reluctant to classical genetic tools like transposable elements or gene mapping. Here, we describe an RNAi-based functional genomic platform that allows the identification of new virulence factors through a forward genetic approach firstly described in Mucorales. This platform contains a whole-genome collection of Mucor circinelloides silenced transformants that presented a broad assortment of phenotypes related to the main physiological processes in fungi, including virulence, hyphae morphology, mycelial and yeast growth, carotenogenesis and asexual sporulation. Selection of transformants with reduced virulence allowed the identification of mcplD, which encodes a Phospholipase D, and mcmyo5, encoding a probably essential cargo transporter of the Myosin V family, as required for a fully virulent phenotype of M. circinelloides. Knock-out mutants for those genes showed reduced virulence in both Galleria mellonella and Mus musculus models, probably due to a delayed germination and polarized growth within macrophages. This study provides a robust approach to study virulence in Mucorales and as a proof of concept identified new virulence determinants in M. circinelloides that could represent promising targets for future antifungal therapies.
    Thematic Areas: Virology Parasitology Molecular biology Microbiology Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Interdisciplinar Immunology Genetics Farmacia Engenharias iii Enfermagem Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências agrárias i Ciência da computação Biotecnología Biodiversidade
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 15537366
    Author's mail: marta.sanchis@urv.cat nadine.alkhoury@estudiants.urv.cat nadine.alkhoury@estudiants.urv.cat nadine.alkhoury@estudiants.urv.cat nadine.alkhoury@estudiants.urv.cat javier.capilla@urv.cat
    Author identifier: 0000-0001-7251-6792 0000-0002-0765-6403
    Record's date: 2024-09-07
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006150
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Plos Pathogens. 13 (1): e1006150-
    APA: Trieu TA, Navarro-Mendoza MI, Pérez-Arques C, Sanchis M, Capilla J, Navarro-Rodriguez P, Lopez-Fernandez L, Torres-Martínez S, Garre V, Ruiz-Vázquez R (2017). RNAi-Based Functional Genomics Identifies New Virulence Determinants in Mucormycosis. Plos Pathogens, 13(1), e1006150-. DOI: 10.1371/journal.ppat.1006150
    Article's DOI: 10.1371/journal.ppat.1006150
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2017
    Publication Type: Journal Publications
  • Keywords:

    Genetics,Immunology,Microbiology,Molecular Biology,Parasitology,Virology
    Responses
    Phospholipase-d
    Oryzae
    Gene
    Fungus
    Expression
    Components
    Clinical-manifestations
    Cells
    Virology
    Parasitology
    Molecular biology
    Microbiology
    Medicina veterinaria
    Medicina iii
    Medicina ii
    Medicina i
    Materiais
    Interdisciplinar
    Immunology
    Genetics
    Farmacia
    Engenharias iii
    Enfermagem
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciências agrárias i
    Ciência da computação
    Biotecnología
    Biodiversidade
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