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Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis

Frédéric Lamoth1, Praveen R Juvvadi2, William J Steinbach3

  • 1Division 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.

Frontiers in Microbiology
|March 13, 2015
PubMed

Insights

New antifungal drug targets are needed for invasive aspergillosis (IA). Histone deacetylases (HDACs) in Aspergillus spp. are crucial for fungal growth and virulence, offering potential as novel therapeutic targets.

Area of Science:

  • Mycology
  • Molecular Biology
  • Drug Discovery

Background:

  • Invasive aspergillosis (IA) is a severe fungal infection with limited treatment options.
  • Current antifungal drugs target fungal cell membranes or walls, facing efficacy issues and resistance.
  • Histone deacetylases (HDACs) regulate fungal gene expression, virulence, and antifungal resistance.

Purpose of the Study:

  • To review the role of HDACs in Aspergillus spp.
  • To explore HDACs as potential novel antifungal drug targets for IA.
  • To discuss the therapeutic potential of HDAC inhibitors against IA.

Main Methods:

  • Literature review of HDACs in Aspergillus spp.
  • Analysis of HDAC contribution to fungal growth, stress response, and virulence.
  • Evaluation of HDAC inhibitors as antifungal agents.

Main Results:

  • HDACs are essential for Aspergillus spp. growth, stress adaptation, and virulence.
  • HDACs regulate non-histone protein acetylation, including Hsp90, impacting antifungal resistance.
  • Specific HDACs in Aspergillus spp. have distinct roles in fungal physiology.

Conclusions:

  • HDACs represent promising novel targets for antifungal drug development against IA.
  • HDAC inhibitors, repurposed from cancer therapy, may offer new treatment strategies for IA.
  • Targeting fungal HDACs could overcome existing antifungal resistance mechanisms.
Keywords:
Aspergillus fumigatusantifungal resistanceantifungal therapyheat shock protein 90lysine deacetylasestrichostatin A

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