Autor según el artículo: 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

Departamento: Ciències Mèdiques Bàsiques

Autor/es 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

Palabras clave: Està en blanc

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.

Grupo de investigación: Unitat de Micologia i Microbiologia Ambiental

Áreas temáticas: Health sciences Ciencias de la salud Ciències de la salut

Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/

ISSN: 1553-7374

Identificador del autor: N/P; N/P; N/P; N/P; N/P; N/P; N/P; N/P; N/P; N/P; N/P

Fecha de alta del registro: 2017-02-16

Volumen de revista: 13

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

DOI del artículo: 10.1371/journal.ppat.1006150

Entidad: Universitat Rovira i Virgili

Año de publicación de la revista: 2017

Página inicial: e1006150

Tipo de publicación: Article Artículo Article