title: Histone deacetylases inhibitors effects on Cryptococcus neoformans major virulence phenotypes.
abstract: Cryptococcus neoformans undergoes phenotypical changes during host infection in order to promote persistence and survival. Studies have demonstrated that such adaptations require alterations in gene transcription networks by distinct mechanisms. Drugs such as the histone deacetylases inhibitors (HDACi) Sodium Butyrate (NaBut) and Trichostatin A (TSA) can alter the chromatin conformation and have been used to modulate epigenetic states in the treatment of diseases such as cancer. In this work, we have studied the effect of NaBut and TSA on the expression of C. neoformans major virulence phenotypes and on the survival rate of an animal model infected with drugs-treated yeasts. Both drugs affected fungal growth at 37°C more intensely than at 30°C; nonetheless, drugs did not affect cell viability at the concentrations we studied. HDACi also provoked the reduction of the fungal capsule expansion. Phospholipases enzyme activity decreased; mating process and melanin synthesis were also affected by both inhibitors. NaBut led to an increase in the population of cells in G2/M. Treated yeast cells, which were washed in order to remove the drugs from the culture medium prior to the inoculation in the Galleria mellonela infection model, did not cause significant difference at the host survival curve when compared to non-treated cells. Overall, NaBut effects on the impairment of C. neoformans main virulence factors were more intense and stable than the TSA effects.
authors.affiliation: a Laboratory of Molecular Biology; Department of Cell Biology; Institute of Biological Sciences; University of Brasilia ; Brasilia , DF , Brazil.
authors.forename: Fabiana As
authors.initials: FA
authors.lastname: Brandão
authors.affiliation: a Laboratory of Molecular Biology; Department of Cell Biology; Institute of Biological Sciences; University of Brasilia ; Brasilia , DF , Brazil.
authors.forename: Lorena S
authors.initials: LS
authors.lastname: Derengowski
authors.affiliation: b Faculty of Ceilandia; University of Brasilia ; Brasilia , DF , Brazil.|c Graduate Program in Tropical Medicine; University of Brasilia ; Brasilia , DF , Brazil.
authors.forename: Patrícia
authors.initials: P
authors.lastname: Albuquerque
authors.affiliation: c Graduate Program in Tropical Medicine; University of Brasilia ; Brasilia , DF , Brazil.|d Graduate Program in Genomic Sciences and Biotechnology; Catholic University of Brasilia ; Brasilia , DF , Brazil.
authors.forename: André M
authors.initials: AM
authors.lastname: Nicola
authors.affiliation: a Laboratory of Molecular Biology; Department of Cell Biology; Institute of Biological Sciences; University of Brasilia ; Brasilia , DF , Brazil.
authors.forename: Ildinete
authors.initials: I
authors.lastname: Silva-Pereira
authors.affiliation: e Laboratory of Gene Regulation and Mutagenesis; Department of Genetics and Morphology; Institute of Biological Sciences; University of Brasilia ; Brasilia , DF , Brazil.
authors.forename: Marcio J
authors.initials: MJ
authors.lastname: Poças-Fonseca
mesh_terms: D000818:Animals; D020148:Butyric Acid / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003455:Cryptococcus neoformans / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology*; D004195:Disease Models, Animal; D062607:Fungal Capsules / Q000187:drug effects / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000378:metabolism; D007915:Lepidoptera; D008543:Melanins / Q000378:metabolism; D050296:Microbial Viability / Q000187:drug effects; D010641:Phenotype; D010740:Phospholipases / Q000032:analysis; D016019:Survival Analysis; D013696:Temperature; D014774:Virulence / Q000187:drug effects
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D008543:Melanins; D020148:Butyric Acid; C012589:trichostatin A; D010740:Phospholipases
keywords: Cryptococcus neoformans; Trichostatin A; chromatin structure; histone deacetylases inhibitors; sodium butyrate; virulence factors