Articles producció científica> Ciències Mèdiques Bàsiques

RNAi-Based Functional Genomics Identifies New Virulence Determinants in Mucormycosis

  • Datos identificativos

    Identificador: imarina:5130748
    Autores:
    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
    Resumen:
    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.
  • Otros:

    Autor según el artículo: 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
    Departamento: Ciències Mèdiques Bàsiques
    Autor/es de la URV: Alkhoury, Nadine / Capilla Luque, Javier / Sanchis Talón, Marta
    Palabras clave: Responses Phospholipase-d Oryzae Gene Fungus Expression Components Clinical-manifestations Cells
    Resumen: 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.
    Áreas temáticas: 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
    Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 15537366
    Direcció de correo del autor: 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
    Identificador del autor: 0000-0001-7251-6792 0000-0002-0765-6403
    Fecha de alta del registro: 2024-09-07
    Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
    Enlace a la fuente original: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006150
    URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referencia al articulo segun fuente origial: Plos Pathogens. 13 (1): e1006150-
    Referencia de l'ítem segons les normes 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
    DOI del artículo: 10.1371/journal.ppat.1006150
    Entidad: Universitat Rovira i Virgili
    Año de publicación de la revista: 2017
    Tipo de publicación: Journal Publications
  • Palabras clave:

    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
  • Documentos:

  • Cerca a google

    Search to google scholar