Cargando…

Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Lamoth, Frédéric, Juvvadi, Praveen R., Steinbach, William J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4329796/
https://www.ncbi.nlm.nih.gov/pubmed/25762988
http://dx.doi.org/10.3389/fmicb.2015.00096
_version_ 1782357492924153856
author Lamoth, Frédéric
Juvvadi, Praveen R.
Steinbach, William J.
author_facet Lamoth, Frédéric
Juvvadi, Praveen R.
Steinbach, William J.
author_sort Lamoth, Frédéric
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4329796
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-43297962015-03-11 Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis Lamoth, Frédéric Juvvadi, Praveen R. Steinbach, William J. Front Microbiol Microbiology 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. Frontiers Media S.A. 2015-02-16 /pmc/articles/PMC4329796/ /pubmed/25762988 http://dx.doi.org/10.3389/fmicb.2015.00096 Text en Copyright © 2015 Lamoth, Juvvadi and Steinbach. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Lamoth, Frédéric
Juvvadi, Praveen R.
Steinbach, William J.
Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis
title Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis
title_full Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis
title_fullStr Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis
title_full_unstemmed Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis
title_short Histone deacetylase inhibition as an alternative strategy against invasive aspergillosis
title_sort histone deacetylase inhibition as an alternative strategy against invasive aspergillosis
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4329796/
https://www.ncbi.nlm.nih.gov/pubmed/25762988
http://dx.doi.org/10.3389/fmicb.2015.00096
work_keys_str_mv AT lamothfrederic histonedeacetylaseinhibitionasanalternativestrategyagainstinvasiveaspergillosis
AT juvvadipraveenr histonedeacetylaseinhibitionasanalternativestrategyagainstinvasiveaspergillosis
AT steinbachwilliamj histonedeacetylaseinhibitionasanalternativestrategyagainstinvasiveaspergillosis