Histone deacetylases inhibitors effects on Cryptococcus neoformans major virulence phenotypes

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 (HDA...

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Bibliographic Details
Published in:Virulence 2015-08, Vol.6 (6), p.618-630
Main Authors: Brandão, Fabiana AS, Derengowski, Lorena S, Albuquerque, Patrícia, Nicola, André M, Silva-Pereira, Ildinete, Poças-Fonseca, Marcio J
Format: Article
Language:English
Subjects:
Animals
Butyric Acid - metabolism
Cell Division - drug effects
chromatin structure
Cryptococcus neoformans
Cryptococcus neoformans - drug effects
Cryptococcus neoformans - growth & development
Cryptococcus neoformans - physiology
Disease Models, Animal
Fungal Capsules - drug effects
Fungal Capsules - metabolism
Histone Deacetylase Inhibitors - metabolism
histone deacetylases inhibitors
Hydroxamic Acids - metabolism
Lepidoptera
Melanins - metabolism
Microbial Viability - drug effects
Phenotype
Phospholipases - analysis
Research Paper
sodium butyrate
Survival Analysis
Temperature
Trichostatin A
Virulence - drug effects
virulence factors
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Summary: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.
ISSN:2150-5594
2150-5608
DOI:10.1080/21505594.2015.1038014