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: Capilla Luque, Javier / Miró Martínez, Eric / 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 javier.capilla@urv.cat 0 0 0

Identificador del autor: 0000-0001-7251-6792 0000-0002-0765-6403

Fecha de alta del registro: 2023-09-23

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: http://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