HDAC genes play distinct and redundant roles in Cryptococcus neoformans virulence

• Published in: Scientific reports Vol. 8; no. 1; pp. 5209 - 17
• Main Authors: Brandão, Fabiana, Esher, Shannon K., Ost, Kyla S., Pianalto, Kaila, Nichols, Connie B., Fernandes, Larissa, Bocca, Anamélia L., Poças-Fonseca, Marcio José, Alspaugh, J. Andrew
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26-03-2018; Nature Publishing Group
• Subjects: 14/63; 38/39; 38/91; 45/41; 45/90; 631/326/193/2542; 631/337/100/102; 631/337/176; 64/60; Animal models; Cell walls; Chromatin remodeling; Cryptococcosis; Cryptococcus neoformans; Fungal infections; Gene expression; Genomes; Histone deacetylase; Humanities and Social Sciences; Macrophages; Melanin; multidisciplinary; Pathogens; Phenotypic plasticity; Science; Science (multidisciplinary); Transcription; Virulence
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-21965-y

The human fungal pathogen
Cryptococcus neoformans
undergoes many phenotypic changes to promote its survival in specific ecological niches and inside the host. To explore the role of chromatin remodeling on the expression of virulence-related traits, we identified and deleted seven genes encoding predicted class I/II histone deacetylases (HDACs) in the
C
.
neoformans
genome. These studies demonstrated that individual HDACs control non-identical but overlapping cellular processes associated with virulence, including thermotolerance, capsule formation, melanin synthesis, protease activity and cell wall integrity. We also determined the HDAC genes necessary for
C
.
neoformans
survival during
in vitro
macrophage infection and in animal models of cryptococcosis. Our results identified the
HDA1
HDAC gene as a central mediator controlling several cellular processes, including mating and virulence. Finally, a global gene expression profile comparing the
hda1Δ
mutant versus wild-type revealed altered transcription of specific genes associated with the most prominent virulence attributes in this fungal pathogen. This study directly correlates the effects of Class I/II HDAC-mediated chromatin remodeling on the marked phenotypic plasticity and virulence potential of this microorganism. Furthermore, our results provide insights into regulatory mechanisms involved in virulence gene expression that are likely shared with other microbial pathogens.