The Set3/Hos2 Histone Deacetylase Complex Attenuates cAMP/PKA Signaling to Regulate Morphogenesis and Virulence of Candida albicans

PLoS Pathogens

Vukoslav Komnenovic¹  Olivia Majer²  Karl Kuchler²  Denes Hnisz²  Ingrid E. Frohner² 

[1] Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria;Medical University Vienna, Christian Doppler Laboratory for Infection Biology, Max F. Perutz Laboratories, Vienna, Austria

关键词: C;    ida albicans;    Adenine;    Histones;    Morphogenesis;    Trehalose;    Yeast infections;    Saccharomyces cerevisiae;    Virulence factors;   

DOI  :  10.1371/journal.ppat.1000889

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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 set3Δ/Δ 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.

【 授权许可】

CC BY