Articles producció científica> Ciències Mèdiques Bàsiques

RNAi-Based Functional Genomics Identifies New Virulence Determinants in Mucormycosis

  • Dades identificatives

    Identificador: PC:2549
    Autors:
    Javier CapillaTrung Anh TrieuMar¿ía Isabel Navarro-MendozaCarlos Pérez-ArquesMarta SanchisPatricia Navarro-RodriguezLoida Lopez-FernandezSantiago Torres-MartínezVictoriano GarreRosa María Ruiz-VázquezFrancisco E. Nicolás
    Resum:
    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.
  • Altres:

    Autor segons l'article: Javier Capilla; Trung Anh Trieu; Mar¿ía Isabel Navarro-Mendoza; Carlos Pérez-Arques; Marta Sanchis; Patricia Navarro-Rodriguez; Loida Lopez-Fernandez; Santiago Torres-Martínez; Victoriano Garre; Rosa María Ruiz-Vázquez; Francisco E. Nicolás
    Departament: Ciències Mèdiques Bàsiques
    Autor/s de la URV: CAPILLA LUQUE, JAVIER; Trung Anh Trieu; Mar¿ía Isabel Navarro-Mendoza; Carlos Pérez-Arques; Marta Sanchis; Patricia Navarro-Rodriguez; Loida Lopez-Fernandez; Santiago Torres-Martínez; Victoriano Garre; Rosa María Ruiz-Vázquez; Francisco E. Nicolás
    Paraules clau: Està en blanc
    Resum: 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.
    Grup de recerca: Unitat de Micologia i Microbiologia Ambiental
    Àrees temàtiques: Health sciences Ciencias de la salud Ciències de la salut
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 1553-7374
    Identificador de l'autor: N/P; N/P; N/P; N/P; N/P; N/P; N/P; N/P; N/P; N/P; N/P
    Data d'alta del registre: 2017-02-16
    Volum de revista: 13
    Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
    Enllaç font original: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006150
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    DOI de l'article: 10.1371/journal.ppat.1006150
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2017
    Pàgina inicial: e1006150
    Tipus de publicació: Article Artículo Article
  • Paraules clau:

    Fongs patògens
    Micosi
    Està en blanc
    Health sciences
    Ciencias de la salud
    Ciències de la salut
    1553-7374
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