title: Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis.
abstract: Invasive aspergillosis (IA) is a life-threatening infection due to Aspergillus fumigatus and other Aspergillus spp. Drugs targeting the fungal cell membrane (triazoles, amphotericin B) or cell wall (echinocandins) are currently the sole therapeutic options against IA. Their limited efficacy and the emergence of resistance warrant the identification of new antifungal targets. Histone deacetylases (HDACs) are enzymes responsible of the deacetylation of lysine residues of core histones, thus controlling chromatin remodeling and transcriptional activation. HDACs also control the acetylation and activation status of multiple non-histone proteins, including the heat shock protein 90 (Hsp90), an essential molecular chaperone for fungal virulence and antifungal resistance. This review provides an overview of the different HDACs in Aspergillus spp. as well as their respective contribution to total HDAC activity, fungal growth, stress responses, and virulence. The potential of HDAC inhibitors, currently under development for cancer therapy, as novel alternative antifungal agents against IA is discussed.
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center , Durham, NC, USA ; Infectious Diseases Service, Department of Medicine, Lausanne University Hospital , Lausanne, Switzerland ; Institute of Microbiology, Lausanne University Hospital , Lausanne, Switzerland.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lamoth
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center , Durham, NC, USA.
authors.forename: Praveen R
authors.initials: PR
authors.lastname: Juvvadi
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center , Durham, NC, USA ; Department of Molecular Genetics and Microbiology, Duke University Medical Center , Durham, NC, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Steinbach
keywords: Aspergillus fumigatus; antifungal resistance; antifungal therapy; heat shock protein 90; lysine deacetylases; trichostatin A