title: Cryptococcus neoformans histone acetyltransferase Gcn5 regulates fungal adaptation to the host.
abstract: Cryptococcus neoformans is an environmental fungus and an opportunistic human pathogen. Previous studies have demonstrated major alterations in its transcriptional profile as this microorganism enters the hostile environment of the human host. To assess the role of chromatin remodeling in host-induced transcriptional responses, we identified the C. neoformans Gcn5 histone acetyltransferase and demonstrated its function by complementation studies of Saccharomyces cerevisiae. The C. neoformans gcn5Delta mutant strain has defects in high-temperature growth and capsule attachment to the cell surface, in addition to increased sensitivity to FK506 and oxidative stress. Treatment of wild-type cells with the histone acetyltransferase inhibitor garcinol mimics cellular effects of the gcn5Delta mutation. Gcn5 regulates the expression of many genes that are important in responding to the specific environmental conditions encountered by C. neoformans inside the host. Accordingly, the gcn5Delta mutant is avirulent in animal models of cryptococcosis. Our study demonstrates the importance of chromatin remodeling by the conserved histone acetyltransferase Gcn5 in regulating the expression of specific genes that allow C. neoformans to respond appropriately to the human host.
authors.affiliation: Department of Medicine, Duke University School of Medicine, 1543 Duke Hospital South, DUMC 3355, Durham, NC 27710, USA.
authors.forename: Teresa R
authors.initials: TR
authors.lastname: O'Meara
authors.forename: Christie
authors.initials: C
authors.lastname: Hay
authors.forename: Michael S
authors.initials: MS
authors.lastname: Price
authors.forename: Steve
authors.initials: S
authors.lastname: Giles
authors.forename: J Andrew
authors.initials: JA
authors.lastname: Alspaugh
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology; D003455:Cryptococcus neoformans / Q000166:cytology / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005656:Fungal Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects; D005816:Genetic Complementation Test; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D009154:Mutation / Q000235:genetics; D021381:Protein Transport / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013312:Stress, Physiological / Q000187:drug effects; D013696:Temperature; D014774:Virulence / Q000187:drug effects; D000099224:p300-CBP-Associated Factor
chemical_list: D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D051548:Histone Acetyltransferases; D029701:Saccharomyces cerevisiae Proteins; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor