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