The Set3/Hos2 histone deacetylase complex attenuates cAMP/PKA signaling to regulate morphogenesis and virulence of Candida albicans.
PLoS Pathog
; 6(5): e1000889, 2010 May 13.
Article
em En
| MEDLINE
| ID: mdl-20485517
ABSTRACT
Candida albicans, like other pleiomorphic fungal pathogens, is able to undergo a reversible transition between single yeast-like cells and multicellular filaments. This morphogenetic process has long been considered as a key fungal virulence factor. Here, we identify the evolutionarily conserved Set3/Hos2 histone deacetylase complex (Set3C) as a crucial repressor of the yeast-to-filament transition. Cells lacking core components of the Set3C are able to maintain all developmental phases, but are hypersusceptible to filamentation-inducing signals, because of a hyperactive cAMP/Protein Kinase A signaling pathway. Strikingly, Set3C-mediated control of filamentation is required for virulence in vivo, since set3Delta/Delta cells display strongly attenuated virulence in a mouse model of systemic infection. Importantly, the inhibition of histone deacetylase activity by trichostatin A exclusively phenocopies the absence of a functional Set3C, but not of any other histone deacetylase gene. Hence, our work supports a paradigm for manipulating morphogenesis in C. albicans through alternative antifungal therapeutic strategies.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Candida albicans
/
Candidíase
/
Proteínas Fúngicas
/
Transdução de Sinais
/
Proteínas Quinases Dependentes de AMP Cíclico
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article