title: The vacuolar-sorting protein Snf7 is required for export of virulence determinants in members of the Cryptococcus neoformans complex.
abstract: Fungal pathogenesis requires a number of extracellularly released virulence factors. Recent studies demonstrating that most fungal extracellular molecules lack secretory tags suggest that unconventional secretion mechanisms and fungal virulence are strictly connected. Proteins of the endosomal sorting complex required for transport (ESCRT) have been recently associated with polysaccharide export in the yeast-like human pathogen Cryptococcus neoformans. Snf7 is a key ESCRT operator required for unconventional secretion in Eukaryotes. In this study we generated snf7Δ mutant strains of C. neoformans and its sibling species C. gattii. Lack of Snf7 resulted in important alterations in polysaccharide secretion, capsular formation and pigmentation. This phenotype culminated with loss of virulence in an intranasal model of murine infection in both species. Our data support the notion that Snf7 expression regulates virulence in C. neoformans and C. gattii by ablating polysaccharide and melanin traffic. These results are in agreement with the observation that unconventional secretion is essential for cryptococcal pathogenesis and strongly suggest the occurrence of still obscure mechanisms of exportation of non-protein molecules in Eukaryotes.
authors.affiliation: 1] Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, Brazil [2].
authors.forename: Rodrigo M da C
authors.initials: RM
authors.lastname: Godinho
authors.affiliation: 1] Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Caixa Postal 15005, Porto Alegre, RS 91501-970, Brazil [2].
authors.forename: Juliana
authors.initials: J
authors.lastname: Crestani
authors.affiliation: Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Caixa Postal 15005, Porto Alegre, RS 91501-970, Brazil.
authors.forename: Lívia
authors.initials: L
authors.lastname: Kmetzsch
authors.affiliation: 1] Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil [2] Laboratório de Biologia, Instituto Nacional de Metrologia, Normalização e Qualidade Industrial (INMETRO), Rio de Janeiro, Brazil.
authors.forename: Glauber de S
authors.initials: Gde S
authors.lastname: Araujo
authors.affiliation: 1] Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil [2] Laboratório de Biologia, Instituto Nacional de Metrologia, Normalização e Qualidade Industrial (INMETRO), Rio de Janeiro, Brazil.
authors.forename: Susana
authors.initials: S
authors.lastname: Frases
authors.affiliation: Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Caixa Postal 15005, Porto Alegre, RS 91501-970, Brazil.
authors.forename: Charley C
authors.initials: CC
authors.lastname: Staats
authors.affiliation: 1] Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Caixa Postal 15005, Porto Alegre, RS 91501-970, Brazil [2] Departamento de Biologia Molecular e Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 91501-970, Brazil.
authors.forename: Augusto
authors.initials: A
authors.lastname: Schrank
authors.affiliation: 1] Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Caixa Postal 15005, Porto Alegre, RS 91501-970, Brazil [2] Departamento de Biologia Molecular e Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 91501-970, Brazil.
authors.forename: Marilene H
authors.initials: MH
authors.lastname: Vainstein
authors.affiliation: 1] Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, 21941-902, Rio de Janeiro, Brazil [2] Fundação Oswaldo Cruz - Fiocruz, Centro de Desenvolvimento Tecnológico em Saúde (CDTS), Rio de Janeiro, Brazil.
authors.forename: Marcio L
authors.initials: ML
authors.lastname: Rodrigues
mesh_terms: D000818:Animals; D003453:Cryptococcosis / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000378:metabolism*; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D005260:Female; D005656:Fungal Proteins / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D011134:Polysaccharides / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology*; D014774:Virulence / Q000502:physiology; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D005656:Fungal Proteins; D011134:Polysaccharides; D037521:Virulence Factors