Histone deacetylase inhibitors may reduce pathogenicity and virulence in Candida albicans.
Candida albicans is able to establish mucosal and invasive diseases by means of different virulence factors that are frequently regulated by epigenetic mechanisms, including the acetylation-deacetylation of histones and of other regulatory proteins. The focus of our work was on understanding the possible effects of several histone deacetylase inhibitors (HDACi) on the expression of phenotypes that are associated with virulence and pathogenicity in C. albicans, such as adhesion to epithelial cells and the yeast to hypha transition. Some of the HDACi used for experiments caused a 90% reduction in the adherence of C. albicans to human cultured pneumocytes and significantly inhibited serum-induced germination. Inhibition of germination was correlated with a significant reduction in transcription of EFG1. Inhibition appeared less evident when an HDA1-deficient strain was tested. These results suggest that selective and specific HDACi could prove to be a valid approach for selected at-risk patients in the combined treatment of infections caused by C. albicans.
Simonetti
Giovanna
G
Department of Public Health Sciences, University of Rome La Sapienza, Rome Italy.
Passariello
Claudio
C
Rotili
Dante
D
Mai
Antonello
A
Garaci
Enrico
E
Palamara
Anna Teresa
AT
D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000472:pathogenicity*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000382:microbiology; D005656:Fungal Proteins / Q000096:biosynthesis; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D025301:Hyphae / Q000254:growth & development; D014157:Transcription Factors / Q000096:biosynthesis; D014774:Virulence / Q000187:drug effects
D000935:Antifungal Agents; D004268:DNA-Binding Proteins; C121438:EFG1 protein, Candida albicans; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D056572:Histone Deacetylase Inhibitors; D014157:Transcription Factors